Ajith Nair

Right ventriculo-arterial coupling in pulmonary hypertension: a magnetic resonance study

Objective To quantify right ventriculo-arterial coupling in pulmonary hypertension by combining standard right heart catheterisation (RHC) and cardiac magnetic resonance (CMR) and to estimate it non-invasively with CMR alone. Design Cross-sectional analysis in a retrospective cohort of consecutive patients. Setting Tertiary care centre. Patients 139 adults referred for pulmonary hypertension evaluation. Interventions CMR and RHC within 2 days (n=151 test pairs). Main outcome measures Right ventriculo-arterial coupling was quantified as the ratio of pulmonary artery (PA) effective elastance (Ea, index of arterial load) to right ventricular maximal end-systolic elastance (Emax, index of contractility). Right ventricular end-systolic volume (ESV) and stroke volume (SV) were obtained from CMR and adjusted to body surface area. RHC provided mean PA pressure (mPAP) as a surrogate of right ventricular end-systolic pressure, pulmonary capillary wedge pressure (PCWP) and pulmonary vascular resistance index (PVRI). Ea was calculated as (mPAP − PCWP)/SV and Emax as mPAP/ESV. Results Ea increased linearly with advancing severity as defined by PVRI quartiles (0.19, 0.50, 0.93 and 1.63 mm Hg/ml/m2, respectively; p<0.001 for trend) whereas Emax increased initially and subsequently tended to decrease (0.52, 0.67, 0.54 and 0.56 mm Hg/ml/m2; p=0.7). Ea/Emax was maintained early but increased markedly with severe hypertension (0.35, 0.72, 1.76 and 2.85; p<0.001), indicating uncoupling. Ea/Emax approximated non-invasively with CMR as ESV/SV was 0.75, 1.17, 2.28 and 3.51, respectively (p<0.001). Conclusions Right ventriculo-arterial coupling in pulmonary hypertension can be studied with standard RHC and CMR. Arterial load increases with disease severity whereas contractility cannot progress in parallel, leading to severe uncoupling.

Non-invasive estimation of pulmonary vascular resistance with cardiac magnetic resonance

AIM To develop a cardiac magnetic resonance (CMR) method for non-invasive estimation of pulmonary vascular resistance (PVR). METHODS AND RESULTS The study comprised 100 consecutive patients with known or suspected pulmonary hypertension (PH; 53 ± 16 years, 73% women) who underwent same-day right heart catheterization (RHC) and CMR. Increased PVR was defined from RHC as >3 WU (n = 66, 66%). From CMR cine and phase-contrast images, right ventricular (RV) volumes and ejection fraction (RVEF), pulmonary artery (PA) flow velocities and areas, and cardiac output were quantified. The best statistical model to estimate PVR was obtained from a derivation cohort (n = 80) based on physiological plausibility and statistical criteria. Validity of the model was assessed in the remaining 20 patients (validation cohort). The CMR-derived model was: estimated PVR (in WU) = 19.38 - [4.62 × Ln PA average velocity (in cm/s)] - [0.08 × RVEF (in %)]. In the validation cohort, the correlation between invasively quantified and CMR-estimated PVR was 0.84 (P < 0.001). The mean bias between the RHC-derived and CMR-estimated PVR was -0.54 (agreement interval -6.02 to 4.94 WU). The CMR model correctly classified 18 (90%) of patients as having normal or increased PVR (area under the receiver operator characteristics curve 0.97; 95% confidence interval: 0.89-1.00). CONCLUSIONS Non-invasive estimation of PVR using CMR is feasible and may be valuable for PH diagnosis and/or follow-up.

Apical right ventricular dysfunction in patients with pulmonary hypertension demonstrated with magnetic resonance

Objective To evaluate segmental right ventricular (RV) dysfunction in pulmonary hypertension (PH) using cardiac magnetic resonance (CMR). Design Cross-sectional analysis in a retrospective cohort of consecutive adult patients. Setting Mount Sinai Hospital in New York. Patients 192 patients with known or suspected PH undergoing right heart catheterisation and CMR. PH was defined as mean pulmonary artery pressure ≥25 mm Hg. Abnormal RV ejection fraction (RVEF) was defined as <50%. Patients were classified into: group 1 (no PH, normal RVEF; n=40), group 2 (PH, normal RVEF; n=41) or group 3 (PH, abnormal RVEF; n=111). Interventions CMR and right heart catheterisation within a 2-week interval. Main outcome measures On cine CMR images, the stack of RV short-axis views was divided into two equal halves. Basal and apical RVEF were calculated using Simpsons method, and a ratio of basal-to-apical RVEF (RVEFratio) was derived. Results Basal RVEF did not differ between groups 1 and 2 (63±8% vs 64±8%; p=1); however, patients in group 2 had significantly lower apical RVEF (46±13% vs 58±10%; p<0.01) and higher RVEFratio (median 1.4 vs 1.1; p<0.01). Both apical and basal RVEF were reduced in group 3 compared with groups 1 and 2 (p<0.01), and the RVEFratio increased with increasing PH severity (p<0.01 for trend). An apical RVEF <50% was more sensitive than global RV dysfunction for the detection of PH. Conclusions Apical dysfunction appears to occur before global RVEF decreases in chronic PH, potentially constituting an early and sensitive marker of RV dysfunction in this setting.

Histopathology of renal failure after heart transplantation: a diverse spectrum.

BACKGROUND Chronic kidney disease occurs frequently after heart transplantation and is associated with significant morbidity and mortality. Herein we describe the histopathology associated with renal failure in a cohort of heart transplant recipients. METHODS Over a 4-year period all patients with an estimated GFR <30 ml/min/1.73 m(2) or significant proteinuria were referred to the kidney transplant clinic for clinical evaluation. A percutaneous renal biopsy was performed as part of a standardized evaluation. RESULTS Eighteen patients underwent renal biopsy 5.8 ± 4.1 years after transplantation. Hypertension (88.9%), Type 2 diabetes (55.6%) and allograft vasculopathy (38.9%) were prevalent. All patients were receiving calcineurin inhibitors. Mean creatinine was 2.9 ± 1.2 mg/dl with an estimated GFR 27.9 ± 9.1 ml/min/1.73 m(2). Eight patients (44%) had proteinuria >1 g per 24 hours. The major histologic findings were nephrosclerosis plus diabetic glomerulopathy (50%), nephrosclerosis and focal segmental glomerulosclerosis (22.2%) and nephrosclerosis alone (22.2%). One patient had direct CNI toxicity consisting of nodular sub-adventitial hyalinosis. Eleven patients (61.1%) had glomerular disease and 11 patients (61.1%) had moderate or severe tubular atrophy. During follow-up, 5 patients (27.8%) started hemodialysis, 4 (22.2%) died, and 2 (11.1%) received a renal transplant. CONCLUSIONS We observed diverse histologic patterns in this series of renal biopsies suggesting that chronic kidney disease after heart transplantation has a complex and varied pathologic basis. Further defining the renal injuries that precede heart transplantation and predispose to the progression of kidney disease after transplant may assist in treating this population.

New index alpha improves detection of pulmonary hypertension in comparison with other cardiac magnetic resonance indices

BACKGROUND Cardiovascular magnetic resonance (CMR) has been proposed for the evaluation of patients with pulmonary hypertension (PH). However, there is no consensus on the optimal method for PH diagnosis using CMR. OBJECTIVE To compare the diagnostic ability of multiple CMR-derived indices for the detection of PH as determined by right heart catheterization (RHC). METHODS A total of 185 patients with known or suspected chronic PH who underwent cardiac CMR and RHC in ≤15 days were included. PH was defined as a mean pulmonary artery (PA) pressure ≥25 mmHg. Right ventricular (RV) volumes, RV ejection fraction (RVEF), PA areas, and PA average blood flow velocity were quantified with CMR. A novel index α was defined as the ratio between minimal PA area and RVEF. RESULTS According to the RHC, PH was present in 152 patients. All CMR-derived parameters correlated with the degree of mean PA pressure, with α having the highest correlation coefficient (r=0.61, p<0.001). Correlations were also highest for α in the patients with pulmonary arterial hypertension (PAH; r=0.55, p<0.001) and non-PAH subgroup (r=0.61, p<0.001). Diagnostic accuracy for the detection of PH, based on receiver operating curve analysis, was best for α (area under the curve=0.95). A cutoff value of 7.2 demonstrated a sensitivity of 90% and a specificity of 88%. CONCLUSIONS An easily-obtainable and novel CMR index α that combines geometrical and functional information of the PA and the RV allows for the noninvasive diagnosis of PH with high accuracy, above other common CMR-derived parameters.

Left ventricular assist devices improve functional class without normalizing peak oxygen consumption.

Heart failure patients supported with left ventricular assist devices (LVAD) enjoy improvements in functional capacity and quality of life. We reasoned that such improvements in exercise capacity should be reflected in an objective increase in peak oxygen consumption as measured by cardiopulmonary exercise testing (CPET). We performed a retrospective review of all recipients of a HeartMate II LVAD at our center from June 2009 to June 2012 who completed CPET. Thirty-seven patients completed CPET an average of 6 months after implantation. Of these, 10 patients had CPET performed before LVAD implantation. Overall, 91.4% of patients improved by at least two New York Heart Association classes, with 34.3% improving by three classes. Postimplant VO2 max was significantly less than predicted (14.7 ± 3.1 vs. 29.8 ± 6.6 ml/kg/min, p < 0.001; percent-predicted 51% ± 12%). For 10 patients with pre- and post-implant studies, VO2 max increased significantly from 11.6 ± 5.0 to 15.4 ± 3.9 ml/kg/min (p = 0.009). VO2 max improves significantly with LVAD support but fails to normalize to predicted values, in spite of improvements in functional class. The severity of preimplantation heart failure does not associate with the degree of VO2 max improvement.

Low Incidence of Bleeding-Related Morbidity With Left Ventricular Assist Device Implantation in the Current Era

Left ventricular assist device (LVAD) implantation is historically associated with high incidence of bleeding-related complications, very high reexploration rates, and frequently massive blood transfusion. Bleeding predisposes to mortality, sepsis, allosensitization, and right ventricular failure. We present results of an integrated approach to reduce bleeding complications. Analysis of 51 implantable LVADs implanted in 50 patients (mean age 52 years; male, 45; Intragency Registry for Mechanically Assisted Circulatory Support [INTERMACS] 1 or 2, 25) in our center in 2008 and 2009, including 15 reoperations. Preoperative coagulopathy was evident in 10 patients. Our strategy included: early LVAD implantation, preoperative nutritional support and hemodynamic optimization, preferential use of continuous flow LVADs, meticulous surgical hemostasis, liberal application of tricuspid annuloplasty, and blood product utilization based on point-of-care testing. Two patients (4%) were reexplored for bleeding. Median transfusion rates intraoperatively were: blood: 2 units (interquartile range [IQR] 0-4); plasma: 0 units (0-2.75); platelets: 0 pools (0-1.75), while postoperative transfusion rates for first 48 h were blood: 1 unit (0-2); plasma: 0 units (0-0.75); and platelets: 0 pools (0,1). Right ventricular assist device was utilized in six patients (11%). Median chest tube drainage in first 24 h was 1230 mL (IQR 862-1687). Median time on ventilator was 2 days, intensive care unit was 6 days, and hospitalization was 18 days. Hospital mortality was 20%. Using an integrated approach, we have experienced bleeding and transfusion rates similar to that seen in non-LVAD complex cardiac operations. The potential to reduce bleeding reduces invasiveness of LVAD surgery, reduces allosensitization, may improve outcomes, and may increase mainstream acceptability of LVADs as definitive therapy for heart failure.

Brain-Heart Interaction in Takotsubo Cardiomyopathy

Takotsubo cardiomyopathy is classically stress induced and characterized by regional wall motion abnormalities in the absence of coronary occlusion. It predominantly affects postmenopausal women; emotional and physical stressors can trigger the classic cardiomyopathic findings. These changes are likely mediated by catecholamines, which cause a distinctive pattern of ventricular dysfunction with a unique pathologic phenotype of apical ballooning. Underlying mood disorders increase the risk for developing takotsubo cardiomyopathy after a triggering event. Takotsubo cardiomyopathy is one of several brain-heart disorders; its unique pathology can shed light on the complex interactions between the brain, sympathetic nervous system, and the cardiovascular system.

Lipid Management in the Geriatric Patient

Elderly individuals are at higher risk for cardiovascular events, and thus this population stands to gain a greater reduction in events from lipid therapy than younger individuals. Multiple primary and secondary prevention trials have demonstrated that the benefits of statins in geriatric patients are equivalent to, or greater than, those seen in younger patients. Combination therapy with non-statin agents should be considered in patients who do not meet cholesterol goals or who have concomitant hypertriglyceridemia or low levels of high-density lipoprotein cholesterol. Although increased side effects may occur with high-dose statin therapy, careful vigilance of drug interactions and limiting polypharmacy can reduce these effects.

Validation of the Prognostic Utility of the Electrocardiogram for Acute Drug Overdose

Background While it is certain that some emergency department patients with acute drug overdose suffer adverse cardiovascular events (ACVE), predicting ACVE is difficult. The prognostic utility of the ECG for heterogeneous drug overdose patients remains to be proven. This study was undertaken to validate previously derived features of the initial ECG associated with ACVE in this population. Methods and Results We performed a prospective validation cohort study to evaluate adult emergency department patients with acute drug overdose at 2 urban university hospitals over 5 years in whom an emergency department admission ECG was performed. Exclusion criteria were alternate diagnoses, anaphylaxis, chronic drug toxicity, and missing outcome data. ACVE was defined as any of the following: circulatory shock, myocardial injury, ventricular dysrhythmia, or cardiac arrest. Blinded cardiologists interpreted ECGs for previously derived predictors of ACVE (ectopy, QT prolongation, nonsinus rhythm, ischemia/infarction), QT dispersion, and prominent R wave in lead AVR. Of 589 patients who met inclusion criteria (48% male, mean age 42), there were 95 ACVEs (39 shock, 64 myocardial injury, 26 dysrhythmia, 16 cardiac arrest). The most common drug exposures were as follows: benzodiazepines, opioids, and acetaminophen. Previously derived criteria were highly predictive of ACVE, with QT correction >500 ms as the highest risk feature (OR 11.2, CI 4.6–27). Conclusions This study confirms that early ECG evaluation is essential to assess the cardiovascular prognosis and medical clearance of emergency department patients with acute drug overdose. Furthermore, this study validates previously derived high‐risk features of the admission ECG to risk stratify for ACVE in this patient population.