A systemic congestive index (systemic pulse pressure to central venous pressure ratio) predicts adverse outcomes in patients undergoing valvular heart surgery.

BACKGROUND AND AIMS: Invasive hemodynamics may provide a more nuanced assessment of cardiac function and risk phenotyping in patients undergoing cardiac surgery. The systemic pulse pressure (SPP) to central venous pressure (CVP) ratio represents an integrated index of right and left ventricular function and thus may demonstrate an association with valvular heart surgery outcomes. This study hypothesized that a low SPP/CVP ratio would be associated with mortality in valvular surgery patients. METHODS: This retrospective cohort study examined adult valvular surgery patients with preoperative right heart catheterization from 2007 through 2016 at a single tertiary medical center (n = 215). Associations between the SPP/CVP ratio and mortality were investigated with univariate and multivariate analyses. RESULTS: Among 215 patients (age 69.7 ± 12.4 years; 55.8% male), 61 died (28.4%) over a median follow-up of 5.9 years. A SPP/CVP ratio <7.6 was associated with increased mortality (relative risk 1.70, 95% confidence interval [CI] 1.08-2.67, p = .019) and increased length of stay (11.56 ± 13.73 days vs. 7.93 ± 4.92 days, p = .016). It remained an independent predictor of mortality (adjusted odds ratio 3.99, 95% CI 1.47-11.45, p = .008) after adjusting for CVP, mean pulmonary artery pressure, aortic stenosis, tricuspid regurgitation, smoking status, diabetes mellitus, dialysis, and cross-clamp time. CONCLUSIONS: A low SPP/CVP ratio was associated with worse outcomes in patients undergoing valvular heart surgery. This metric has potential utility in preoperative risk stratification to guide patient selection, prognosis, and surgical outcomes.

Increased left and right atrial volume indices are associated with decreased survival times post-cardiac arrest.

BACKGROUND: Left and right atrial volume indices (LAVI and RAVI) are markers of cardiac remodeling. LAVI and RAVI are associated with worse outcomes in other cardiac conditions. This study aimed to determine the associations of these atrial volume indices with survival time post-cardiac arrest. METHODS: This was a single center, retrospective study of patients with a sudden cardiac arrest event during index hospitalization from 2014-2018 based on pre-arrest parameters. The analysis was stratified based on whether a pulseless ventricular tachycardia/ventricular fibrillation (pVT/VF) event or a pulseless electrical activity (PEA)/asystole event occurred. Cox proportional hazards regression and model selection with best subsets approach evaluated the association of atrial volume parameters with survival times in the context of other covariates. RESULTS: Of 305 patients studied (64 ± 14 years, 37% female), the mean LAVI was 34.0 ± 15.8 mL/m2 (based on 162 reliable measurements), and mean RAVI was 25.0 ± 15.6 mL/m2 (based on 163 measurements). Increased atrial volume indices were most strongly associated with survival in patients who had sustained pVT/VF (LAVI HR 0.47, 95% CI 0.25-0.90, p = 0.020; RAVI HR 0.57, 95% CI 0.30-1.05, p = 0.074). In multivariable best subsets Cox regression with LAVI, RAVI, and 13 other scaled covariates, LAVI < 34 ml/m2 was by far the best single predictor of survival (p < 0.0001), and the next best predictor was the absence of pulmonary hypertension. CONCLUSION: Among patients with cardiac arrest from ventricular arrhythmias, those with no more than mild left atrial enlargement pre-arrest by LAVI measurement had the best prognosis. Additional studies are indicated to validate the importance of this finding for clinical management decisions. CONDENSED ABSTRACT: In patients with sudden cardiac arrest associated with ventricular arrhythmias, a left atrial volume index (LAVI) < 34 mL/m2 prior to the arrest had the strongest association with survival among fifteen candidate predictors. Pulmonary hypertension was more common in patients with an elevated right atrial volume index (RAVI), and the absence of pulmonary hypertension was the next best pre-arrest parameter predictive of survival. Larger studies are indicated to validate the use of LAVI for clinical management decisions in this condition.

A rapid electromechanical model to predict reverse remodeling following cardiac resynchronization therapy.

Cardiac resynchronization therapy (CRT) is an effective therapy for patients who suffer from heart failure and ventricular dyssynchrony such as left bundle branch block (LBBB). When it works, it reverses adverse left ventricular (LV) remodeling and the progression of heart failure. However, CRT response rate is currently as low as 50-65%. In theory, CRT outcome could be improved by allowing clinicians to tailor the therapy through patient-specific lead locations, timing, and/or pacing protocol. However, this also presents a dilemma: there are far too many possible strategies to test during the implantation surgery. Computational models could address this dilemma by predicting remodeling outcomes for each patient before the surgery takes place. Therefore, the goal of this study was to develop a rapid computational model to predict reverse LV remodeling following CRT. We adapted our recently developed computational model of LV remodeling to simulate the mechanics of ventricular dyssynchrony and added a rapid electrical model to predict electrical activation timing. The model was calibrated to quantitatively match changes in hemodynamics and global and local LV wall mass from a canine study of LBBB and CRT. The calibrated model was used to investigate the influence of LV lead location and ischemia on CRT remodeling outcome. Our model results suggest that remodeling outcome varies with both lead location and ischemia location, and does not always correlate with short-term improvement in QRS duration. The results and time frame required to customize and run this model suggest promise for this approach in a clinical setting.

The Future of Cardiac Magnetic Resonance Clinical Trials.

Over the past 2 decades, cardiac magnetic resonance (CMR) has become an essential component of cardiovascular clinical care and contributed to imaging-guided diagnosis and management of coronary artery disease, cardiomyopathy, congenital heart disease, cardio-oncology, valvular, and vascular disease, amongst others. The widespread availability, safety, and capability of CMR to provide corresponding anatomical, physiological, and functional data in 1 imaging session can improve the design and conduct of clinical trials through both a reduction of sample size and provision of important mechanistic data that may augment clinical trial findings. Moreover, prospective imaging-guided strategies using CMR can enhance safety, efficacy, and cost-effectiveness of cardiovascular pathways in clinical practice around the world. As the future of large-scale clinical trial design evolves to integrate personalized medicine, cost-effectiveness, and mechanistic insights of novel therapies, the integration of CMR will continue to play a critical role. In this document, the attributes, limitations, and challenges of CMR's integration into the future design and conduct of clinical trials will also be covered, and recommendations for trialists will be explored. Several prominent examples of clinical trials that test the efficacy of CMR-imaging guided pathways will also be discussed.

MAGGIC, STS, and EuroSCORE II Risk Score Comparison After Aortic and Mitral Valve Surgery.

OBJECTIVES: To compare the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score with the established Society of Thoracic Surgeons (STS) and EuroSCORE II risk prediction models regarding mortality discrimination after aortic and mitral valve surgery. DESIGN: Retrospective cohort study. SETTING: Single tertiary academic medical center. PARTICIPANTS: A total of 259 patients who underwent open aortic valve replacement or open mitral valve repair/replacement from 2009-2014. INTERVENTIONS: Retrospective chart review. MEASUREMENTS AND MAIN RESULTS: MAGGIC, STS, and EuroSCORE II risk scores for each patient were studied using binary logistic regression and receiver operating characteristic analysis for the primary endpoint of one-year mortality and secondary endpoint of 30-day mortality. One-year mortality C-statistics were similar across risk scores (STS 0.709, 95% confidence interval [CI] 0.578-0.841; MAGGIC 0.673, 95% CI 0.547-0.799; EuroSCORE II 0.642, 95% CI 0.521-0.762; p = 0.56 between STS and MAGGIC; p = 0.20 between STS and EuroSCORE II; and p = 0.69 between MAGGIC and EuroSCORE II). Thirty-day mortality C-statistics also were similar between STS (0.797, 95% CI 0.655-0.939; p < 0.0001 v null hypothesis), MAGGIC (0.721, 95% CI 0.581-0.860; p = 0.33 v STS), and EuroSCORE II (0.688, 95% CI 0.557-0.818; p = 0.06 v STS; p = 0.68 v MAGGIC). CONCLUSIONS: The MAGGIC risk score performs similarly to STS and EuroSCORE II risk models in mortality discrimination after aortic and mitral valve surgery, albeit in a small sample size. This finding has important implications in establishing MAGGIC as a viable prognostic model in this population subset, with fewer variables and ease of use representing key advantages over STS and EuroSCORE II.

Haemodynamically Derived Pulmonary Artery Pulsatility Index Predicts Mortality in Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary artery (PA) pulsitility index (PAPi) is a novel haemodynamic index shown to predict right ventricular failure in acute inferior myocardial infarction and post left ventricular assist device surgery. We hypothesised that PAPi calculated as [PA systolic pressure - PA diastolic pressure]/right atrial pressure (RAP) would be associated with mortality in the National Institutes of Health Registry for Primary Pulmonary Hypertension (NIH-RPPH). METHODS: The impact of PAPi, the Pulmonary Hypertension Connection (PHC) risk score, right ventricular stroke work, pulmonary artery capacitance (PAC), other haemodynamic indices, and demographic characteristics was evaluated in 272 NIH-RPPH patients using multivariable Cox proportional hazards (CPH) regression and receiver operating characteristic (ROC) analysis. RESULTS: In the 272 patients (median age 37.7+/-15.9years, 63% female), the median PAPi was 5.8 (IQR 3.7-9.2). During 5years of follow-up, 51.8% of the patients died. Survival was markedly lower (32.8% during the first 3years) in PAPi quartile 1 compared with the remaining patients (58.5% over 3years in quartiles 2-4; p<0.0001). The best multivariable CPH survival model included PAPi, the PHC-Risk score, PAC, and body mass index (BMI). In this model, the adjusted hazard ratio for death with increasing PAPi was 0.946 (95% CI 0.905-0.989). The independent ROC areas for 5-year survival based on bivariable logistic regression for PAPi, BMI, PHC Risk, and PAC were 0.63, 0.62, 0.64, and 0.65, respectively (p<0.01). The ROC area for 5-year survival for the multivariable logistic model with all four covariates was 0.77 (p<0.0001). CONCLUSIONS: Pulmonary artery pulsatility index was independently associated with survival in PAH, highlighting the utility of PAPi in combination with other key measures for risk stratification in this population.

Preoperative Invasive Hemodynamic Determinants of Survival Among Patients Undergoing Aortic or Mitral Valve Surgery.

OBJECTIVES: To evaluate the association of preoperative invasive hemodynamic parameters with mortality in valvular heart surgery. DESIGN: Retrospective cohort study. SETTING: Single tertiary academic medical center. PARTICIPANTS: A total of 382 patients who underwent preoperative right and/or left heart catheterization before open aortic valve replacement (AVR), open mitral valve repair/replacement (MVR), or combined AVR and MVR, from July 2009 to December 2014. INTERVENTIONS: Retrospective chart review. MEASUREMENTS AND MAIN RESULTS: Common hemodynamic indices derived from direct catheterization measurements were assessed, including pulmonary artery systolic pressure (PASP), pulmonary artery pulse pressure (PPP), mean pulmonary capillary wedge pressure (mPCWP), pulmonary artery pulsatility index, diastolic pressure gradient, left ventricular work index, and right ventricular work index. Bivariable and multivariable associations of these measures with survival were determined using Cox proportional hazards regression. Kaplan-Meier survival curves were generated using the log-rank test. The median age of the cohort was 69 years (interquartile range 60-79 years), and 162 (42.4%) of the patients were female. Elevated PASP (hazard ratio [HR] 1.32 per 10 mmHg, p < 0.0001), elevated PPP (HR 1.48 per 10 mmHg, p < 0.0001), and elevated mPCWP (HR 1.95 per 10 mmHg, p < 0.0001) were all associated with decreased survival, as was decreased diastolic blood pressure (DBP) (p = 0.005). The combination of elevated PPP and decreased DBP was associated with the worst outcomes. CONCLUSIONS: PASP, PPP, mPCWP, and DBP were significantly associated with mortality in valvular heart surgery patients. These hemodynamic parameters may be useful in risk stratification of this population subset.

Postprocedure mapping of cardiac resynchronization lead position using standard fluoroscopy systems: implications for the nonresponder with scar.

BACKGROUND: The relationship between cardiac resynchronization therapy (CRT), left ventricular (LV) lead position, scar, and regional mechanical function influences CRT response. OBJECTIVE: To determine LV lead position relative to LV structural characteristics in standard clinical practice, we developed and validated a practical yet mathematically rigorous method to register procedural fluoroscopic LV lead position with pre-CRT cardiac magnetic resonance (CMR). METHODS: After one-time calibration of the standard fluoroscopic suite, we identified the projected CMR LV lead position using three reference landmarks on both CMR and fluoroscopy. This predicted lead position was validated in a canine model by histology and in eight "validation group" patients based on postoperative computed tomography scans (n = 7) or CMR coronary sinus venography (n = 1). The methodology was applied in an additional eight patients with CRT nonresponse and infarction-related myocardial scar. RESULTS: The projected and actual lead positions were within 1.2 mm in the canine model. The median distance between projected and actual lead positions for the validation group (n = 8) and animal validation case was 11.3 mm (interquartile range 9.2-14.6 mm). In the application (nonresponder) group (n = 8), the lead mapped to the scar periphery in three patients, the core of the scar in one patient, and more than 3 cm from scar in four patients. CONCLUSIONS: This methodology projects procedural fluoroscopic LV lead position onto pre-CRT CMR using standard fluoroscopic equipment and a one-time calibration, enabling assessment of LV lead position with sufficient accuracy to identify the lead position relative to regional function and infarction-related scar in CRT nonresponders.

Initial experience of sequential surgical epicardial-catheter endocardial ablation for persistent and long-standing persistent atrial fibrillation with long-term follow-up.

BACKGROUND: Patients with long-standing persistent (LSP) atrial fibrillation (AF) who have previously undergone catheter ablation represent a challenging patient population. Repeat catheter ablation in these patients is arduous and associated with a high failure rate, whereas surgical ablation can be complicated by multiple flutters. We sought to determine if minimally-invasive surgical ablation, followed by catheter ablation of all inducible flutters, would improve success rates over repeat catheter ablation alone. METHODS: Fifteen patients (Sequential) with persistent or LSP AF who failed at least one catheter ablation and one anti-arrhythmic drug (AAD) underwent surgical ablation, followed by planned endocardial evaluation and catheter mapping with ablation during the same hospitalization. Sequential patients were matched to 30 patients who had previously failed at least one catheter ablation and underwent a repeat catheter ablation (catheter-alone). The primary end point was event-free survival of any documented AF recurrence or AAD use. RESULTS: All patients underwent uncomplicated surgical ablation and electrophysiology procedure. Five Sequential patients had seven inducible flutters that were mapped and ablated. After a mean follow-up of 20.7±4.5 months, 13/15 (86.7%) Sequential patients, but only 16/30 (53.3%) catheter-alone patients, were free of any atrial arrhythmia and off of AAD (p=0.04). On AAD, 14/15 (93.3%) Sequential patients were free of any atrial arrhythmia recurrence, compared to 17/30 (56.7%) catheter-alone patients (p=0.01). CONCLUSIONS: For patients with atrial fibrillation who have failed catheter ablation, Sequential minimally invasive epicardial surgical ablation, followed by endocardial catheter-based ablation, has a higher early success rate than repeat catheter ablation alone.

Physiology of biventricular pacing.

Biventricular pacing (cardiac resynchronization therapy ) has been shown to be a very effective therapy for patients with heart failure and dyssynchrony, with improved survival now shown in a recent trial. Electrical dyssynchrony, usually quantified by the duration of the QRS complex, is distinct from mechanical dyssynchrony. Intraventricular mechanical dyssynchrony is most commonly manifest by decreased septal work with concomitant early lateral wall prestretch and subsequent inefficient late contraction. Intraventricular dyssynchrony appears to be more predictive of response to CRT than interventricular dyssynchrony. Mechanical left ventricular dyssynchrony also is associated with regional molecular derangements in connexin-43, stress response kinases, and tumor necrosis factor-alpha. These molecular derangements may lead to abnormalities in conduction velocity and action potential duration, which may predispose to ventricular arrhythmia. Biventricular pacing corrects abnormal regional wall stresses and results in electrical, mechanical, and molecular left ventricular remodeling.

Circumferential ablation with pulmonary vein isolation in permanent atrial fibrillation.

Each of the main approaches to catheter ablation of atrial fibrillation (AF, segmental and circumferential) is associated with limited efficacy in patients with permanent AF. The objective is to report outcomes of circumferential ablation with pulmonary vein (PV) isolation, determined using a circular mapping catheter, in patients with permanent AF and determine relations between the duration of permanent AF and efficacy. The patient population was composed of 41 consecutive patients (34 men; age 58 +/- 11 years) with permanent AF who underwent radiofrequency catheter ablation through circumferential ablation with PV isolation. They were in permanent AF for 2.3 +/- 3.6 years, and 3.4 +/- 2.2 cardioversion procedures and 1.9 +/- 0.8 class I/III antiarrhythmic drugs had failed. After a follow-up of 11 +/- 2 months, the single-procedure success rate was 36% (n = 15) with an additional 12% (n = 5) showing improvement. With repeat procedures in 19%, the success rate was 54% (n = 22) with an additional 12% (n = 5) showing improvement. All patients who underwent repeat ablations had recovered PV conduction. Single-procedure success was higher in patients who were in permanent AF for < or =1 year compared with those in permanent AF for >1 year (50% vs 20%, respectively, p = 0.05). A major complication occurred in 4 patients (8%), including 3 patients with vascular complications and 1 with stroke. In conclusion, study results suggest that circumferential ablation with PV isolation has moderate efficacy in patients with permanent AF. Efficacy is limited in those in continuous AF for >12 months.

Heart failure-associated alterations in troponin I phosphorylation impair ventricular relaxation-afterload and force-frequency responses and systolic function.

Recent studies have found that selective stimulation of troponin (Tn)I protein kinase A (PKA) phosphorylation enhances heart rate-dependent inotropy and blunts relaxation delay coupled to increased afterload. However, in failing hearts, TnI phosphorylation by PKA declines while protein kinase C (PKC) activity is enhanced, potentially augmenting TnI PKC phosphorylation. Accordingly, we hypothesized that these site-specific changes deleteriously affect both rate-responsive cardiac function and afterload dependence of relaxation, both prominent phenotypic features of the failing heart. A transgenic (TG) mouse model was generated in which PKA-TnI sites were mutated to mimic partial dephosphorylation (Ser22 to Ala; Ser23 to Asp) and dominant PKC sites were mutated to mimic constitutive phosphorylation (Ser42 and Ser44 to Asp). The two highest-expressing lines were further characterized. TG mice had reduced fractional shortening of 34.7 +/- 1.4% vs. 41.3 +/- 2.0% (P = 0.018) and slight chamber dilation on echocardiography. In vivo cardiac pressure-volume studies revealed near doubling of isovolumic relaxation prolongation with increasing afterload in TG animals (P < 0.001), and this remained elevated despite isoproterenol infusion (PKA stimulation). Increasing heart rate from 400 to 700 beats/min elevated contractility 13% in TG hearts, nearly half the response observed in nontransgenic animals (P = 0.005). This blunted frequency response was normalized by isoproterenol infusion. Abnormal TnI phosphorylation observed in cardiac failure may explain exacerbated relaxation delay in response to increased afterload and contribute to blunted chronotropic reserve.

Use of a coronary sinus lead and biventricular ICD to correct a sensing abnormality in a patient with arrhythmogenic right ventricular dysplasia/cardiomyopathy.

Implantable cardioverter defibrillators (ICDs) are frequently offered to patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). Yet ICDs in these patients may be complicated by poor sensed amplitudes resulting from fatty and fibrous tissue replacement of right ventricular myocardium. We present the case of a patient with ARVD/C who had inappropriate detection of ventricular tachycardia with a single-chamber ICD due to poor sensed right ventricular amplitudes. We discuss how the use of a bipolar coronary sinus lead and a biventricular ICD generator with a novel header configuration solved the problem.