Surgical Pericardiectomy for Constrictive Pericarditis: A Single Tertiary Center Experience.

BACKGROUND: Although surgery is the sole therapeutic option for patients with constrictive pericarditis (CP), reports on high postoperative mortality rates have led to hesitant surgery referral. The aim of this study was to report the short- and long-term outcomes of surgical pericardiectomy (SP) from a large tertiary center. METHODS: Between January 2005 and January 2017, 55 consecutive patients underwent SP after comprehensive echocardiography, computed tomography, and hemodynamic studies. Detailed clinical, imaging, surgical techniques and follow-up outcomes were recorded. RESULTS: The most common etiology was idiopathic (n = 27, 49%) and 33 patients (60%) were in functional class 3/4. Sixteen patients (29%) underwent concomitant interventions during SP, and cardiopulmonary bypass (CPB) was used in these, as well as in four additional cases. Complete resection, independent of CPB, was achieved in 96%. One patient died during the index hospitalization, and four (7%) needed re-explorations due to bleeding. While 12 patients (22%) died during a mean follow-up of 52 ± 39 months, only 1 death was due to right heart failure. Functional class significantly improved (with a p-value < 0.001), diuretics were discontinued in all, and significant reductions of right atrial pressures were recorded. None of these outcomes differed as a result of concomitant interventions at the time of SP. CONCLUSION: Short- and long-term outcomes of SP, performed either alone or concomitantly with other procedures, indicate high safety and favorable clinical and hemodynamic efficacy for the treatment of CP.

Participation in an Exercise-Based Cardiac Rehabilitation Program and Functional Improvement of Heart Failure Patients with Preserved Versus Reduced Left Ventricular Systolic Function.

BACKGROUND: About half of all patients with heart failure are diagnosed with heart failure preserved ejection fraction (HFpEF). Until now, studies have failed to show that medical treatment improves the prognosis of patients with HFpEF. OBJECTIVES: To evaluate changes in exercise capacity of patients with HFpEF compared to those with heart failure with reduced ejection fraction (HFrEF) following an exercise training program. METHODS: Patient data was retrieved from a multi-center registry of patients with heart failure who participated in a cardiac rehabilitation program. Patients underwent exercise testing and an echocardiogram prior to entering the program and were retested6  months later. RESULTS: Of 216 heart failure patients enrolled in the program, 170 were diagnosed with HFrEF and 46 (21%) with HFpEF. Patients with HFpEF had lower baseline exercise capacity compared to those with HFrEF. Participating in a 6 month exercise program resulted in significant and similar improvement in exercise performance of both HFpEF and HFrEF patients: an absolute metabolic equivalent (MET) change (1.45 METs in HFrEF patients vs. 1.1 in the HFpEF group, P = 0.3). CONCLUSIONS: An exercise training program resulted in similar improvement of exercise capacity in both HFpEF and HFrEF patients. An individualized, yet similarly structured, cardiac rehabilitation program may serve both heart failure groups, providing safety and efficacy.

Comparison of acute kidney injury classifications in patients undergoing transcatheter aortic valve implantation: Predictors and long-term outcomes.

BACKGROUND: Acute kidney injury (AKI) was demonstrated to adversely affect outcome in patients undergoing transcatheter aortic valve implantation (TAVI). We compared predictors for AKI and associated outcomes according to various definitions among patients undergoing TAVI in a tertiary medical center. METHODS: Two-hundred and seventeen TAVI patients were evaluated for the occurrence of AKI according to Kidney Disease Improving Global Outcomes (KDIGO)/Valve Academic Research Consortium (VARC-2) and Risk Injury Failure Loss End-Stage (RIFLE) definitions. Multivariate analysis was conducted to assess predictors of AKI. Cox hazard ratio was used to evaluate long-term mortality in this patient population. RESULTS: AKI occurred in 23 and 21% of patients (n = 49, n = 46) according to KDIGO/VARC-2 and RIFLE definitions, respectively, with an approximate 10% of disagreement between both systems. Predictors of AKI according to KDIGO/VARC-2 were chronic obstructive pulmonary disease (COPD; OR = 2.66, P = 0.01), PVD (OR = 3.45, P = 0.02) and a lower baseline eGFR (OR = 1.03 per 1 mL/min/1.73 m(2) decrease, P = 0.02). While BMI (OR = 1.12, P = 0.01), prior ischemic heart disease (OR = 2.35, P = 0.04) and COPD (OR = 2.18, P = 0.04) were associated with AKI as defined by the RIFLE definition. AKI defined by either classification was independently associated with long-term mortality (HR = 1.63, for the KDIGO/VARC-2 definition and HR = 1.60 for RIFLE definition, P = 0.04 for both models), with borderline superiority of the KDIGO/VARC-2 classification. CONCLUSIONS: Different clinical characteristics predict the occurrence of AKI after TAVI when RIFLE and KDIGO/VARC-2 classifications are used. Both classification systems of AKI identify patients with increased risk for long-term mortality, with superiority of the KDIGO/VARC-2 definition, which should be used for AKI grading.

Vascular complications in steroid treated patients undergoing transfemoral aortic valve implantation.

OBJECTIVE: To assess the rate of Vascular complications in steroid treated patients undergoing transfemoral aortic valve implantation (TAVI). BACKGROUND: Steroid therapy has been associated with increased post-surgical bleeding. Vascular complications are a major concern in patients undergoing TAVI. However, the effect of corticosteroids on vascular complications has not been assessed in these patients. METHODS: We conducted a retrospective analysis of 220 consecutive patients undergoing transfemoral TAVI at our institute between 2009 and 2013. Patients who were on steroids at the time of the procedure (n = 25) were compared with those who were not (n = 195). RESULTS: Baseline characteristics between groups were similar except for greater incidence of chronic renal failure (52 vs. 25%, P = 0.05) and lower left ventricular ejection fraction (50.3 vs. 55.8%, P = 0.037) in the steroid group. The rate of procedural success and nonvascular complication were similar in both groups with the exception of more temporary AV block in the steroid group (24 vs. 8%, P = 0.016). Patients treated with steroids had significantly more minor vascular complication (44 vs. 23%, P = 0.024), and significantly more femoral artery stenosis (16 vs. 5%, P = 0.036), occlusion (8 vs. 1%, P = 0.014), need for femoral artery percutaneous transluminal angioplasty (PTA) (32 vs. 12%, P = 0.009), and femoral artery PTA or stenting (32% vs. 15%, P = 0.031). On multivariate analysis steroid treatment was the only predictor of minor vascular complications (RR=2.65, 95% CI 1.04-6.8, P = 0.042). CONCLUSIONS: Concurrent corticosteroid treatment is associated with a higher rate of minor vascular complication following transfemoral TAVI. Operators should be aware of this risk when assessing patients for the procedure.

Clinical impact of diabetes mellitus in patients undergoing transcatheter aortic valve replacement.

BACKGROUND: Diabetes mellitus (DM) and aortic stenosis (AS) are frequent findings in the elderly population. Data regarding the influence of DM on the outcomes of patients undergoing transcatheter aortic valve replacement (TAVR) due to AS are limited. The aim of this study was to examine the impact of DM on TAVR outcomes. METHODS: We investigated 443 patients with severe AS undergoing TAVR. Subjects were divided into insulin-dependent diabetic mellitus (IDDM) patients (N = 44), non-dependent insulin diabetic mellitus (NIDDM) patients (N = 114) and non-diabetics (N = 285) of whom 31 (74%), 86 (79%) and 209 (76%) respectively had trans-femoral TAVR. Peri-procedural complications and outcomes were recorded according to the Valve Academic Research Consortium-2 criteria. RESULTS: Patients with IDDM as well as NIDDM demonstrated similar complication rates compared with non-diabetic patients, except for acute kidney injury (AKI) grade 3 [4 (2%) and 3 (3%) vs. 1 (0.4%) respectively, p = 0.032]. Kaplan-Meier survival analysis showed that DM, regardless of the type of treatment, was not associated with increased 2 years mortality (Log-rank p value 0.44). Multivariate cox regression analysis adjusted for age, gender, coronary artery disease, DM, AKI3, hypertension, chronic renal failure and peripheral vascular disease found that AKI3 was associated with increased risk of 2 years mortality [HR = 7.35, 95% CI 2.16-25.07, p = 0.001] whereas female gender was found as a protective factor [HR = 0.47, 95% CI 0.28-0.8, p = 0.005], and DM was not associated with increased risk. CONCLUSIONS: Following TAVR, DM patients seem to have similar peri-procedural and mid-term outcomes compared with patients without DM, while IDDM patients seem to suffer greater incidence of AKI. Further research in larger cohorts of patients is needed to validate our results.

MitraClip implantation for high risk patients with severe mitral regurgitation: the Sheba experience.

BACKGROUND: Percutaneous edge-to-edge mitral valve repair using the MitraClip system has evolved as a new tool in the treatment of mitral regurgitation (MR). OBJECTIVES: To present our initial experience with MitraClip implantation in 20 high risk patients at Sheba Medical Center. METHODS: Twenty high surgical risk patients with symptomatic significant MR underwent MitraClip implantation. Clinical and echocardiographic parameters were recorded at baseline and at follow-up. RESULTS: The patients' mean age was 76 years and 65% were male. Coronary artery disease was present in 85% and 45% ent in had previous bypass surgery. Renal failure was present in 65%, atrial fibrillation in 60%, and 30% had an implantable cardioverter defibrillator/cardiac resynchronization therapy device. Mean left ventricular ejection fraction was 36%. Grade III-IV MR was present in all patients with the vast majority suffering from functional MR secondary to ventricular remodeling. New York Heart Association (NYHA) class was III-IV in 90%. Patients were followed for a mean of 231 days. Acute reduction of MR grade to < or = 2 was accomplished in 19 of the 20 patients (95%) with a 30 day mortality of 5%. At follow-up MR was reduced to < or = 2 in 64% of patients, and NYHA class improved in 70% of patients. An additional 2 patients (11%) died during follow-up. CONCLUSIONS: MitraClip implantation is feasible and safe in high risk highly symptomatic patients with significant MR. Acute and mid-term results are comparable to similar high risk patient cohorts in the literature. Continued surveillance and longer follow-up are needed to elucidate which patients are most likely to benefit from the procedure.

Trans-catheter aortic valve implantation for non-classical indications.

BACKGROUND: Trans-catheter aortic valve implantation (TAVI) has emerged as a novel therapeutic approach for patients with severe tricuspid aortic stenosis (AS) not suitable for aortic valve replacement. OBJECTIVES: To describe our initial single-center experience with TAVI in patients with "off-label" indications. METHODS: Between August 2008 and December 2011 we performed TAVI in 186 patients using trans-femoral, transaxillary, trans-apical and trans-aortic approaches. In 11 patients (5.9%) TAVL was undertaken due to: a) pure severe aortic regurgitation (AR) (n = 2), b) prosthetic aortic valve (AV) failure (n = 5), c) bicuspid AV stenosis (n = 2), and d) prosthetic valve severe mitral regurgitation (MR) (n = 2). RESULTS: Implantation was successful in all: six patients received a CoreValve and five patients an Edwards-Sapien valve. In-hospital mortality was 0%. Valve hemodynamics and function were excellent in all patients except for one who received an Edwards-Sapien that was inside a Mitroflow prosthetic AV and led to consistently high trans-aortic gradients. No significant residual regurgitation in AR and MR cases was observed. CONCLUSIONS: TAVI is a good alternative to surgical AV replacement in high risk or inoperable patients with severe AS. TAVI for non-classical indications such as pure AR, bicuspid AV, and failed prosthetic aortic and mitral valves is feasible and safe and may be considered in selected patients.

Blood lipid levels and treatment following an acute coronary syndrome or coronary intervention - Journey from hospital to cardiac rehabilitation.

Background: A significant number of coronary artery disease patients do not attain guideline recommended LDL levels. Participating in a cardiac rehabilitation (CR) program has been shown to improve adherence to medical therapy. Objectives: Evaluate the specific lipid lowering therapy (LLT) prescribed and percent of subjects achieving LDL levels of <70 mg/dL before and after 3 months following CR program initiation. Methods: From May 2017 to April 2019, we prospectively recruited patients referred to our CR program and compared 1015 of them at 4 time points; (P1) just prior to the index hospitalization, (P2) during the index hospitalization, (P3) upon entering the CR program, roughly 3 months after the index hospitalization, and (P4) 3 months into the CR program. Included in the analysis were parameters of lipid levels, the dispensed medication given, as well as patient adherence to treatment. Results: At CR intake, LDL goals were partially achieved with 57% of patients below 70 mg/dL. After completion of 3 months of CR, 63% of patients had LDL levels below 70 mg/dL, despite the fact that the majority (95%) were prescribed high-dose potent statins. Aside from the LDL levels at CR intake, we found no other independent predictors for not attaining the lipid goals at 6 months. Conclusions: A significant treatment gap is present even in a selected population participating in CR, with the vast majority receiving guideline recommended LLT. In order to improve goals, we need to intensify LLT treatment, and increase patient adherence to therapy.

The Association of Severe Tricuspid Regurgitation with Poor Survival Is Modified by Right Ventricular Pressure and Function: Insights from SHEBAHEART Big Data.

BACKGROUND: Contemporary data on the independent association of severe tricuspid regurgitation (TR) with excess mortality are needed. The aims of this study were to describe contemporary outcomes of patients with severe TR and to identify outcome modifiers. METHODS: Consecutive echocardiographic reports linked to clinical data from the largest medical center in Israel (2007-2019) were reviewed. The primary outcome was all-cause mortality. Cox regression and propensity score matching models were applied. RESULTS: The final cohort included 97,096 patients. Mild, moderate, and severe TR was documented in 27,147 (28%), 2,844 (3%) and 1,805 (2%) patients, respectively. During a median follow-up period of 5 years (interquartile range, 2-8 years), 22,170 patients (23%) died. Kaplan-Meier survival analysis demonstrated an increased risk for death with an increasing degree of TR (log-rank P < .001). Propensity score matching of 1,265 patients with severe TR and matched control subjects showed that compared with those with nonsevere TR, patients with severe TR were 17% more likely to die (95% CI, 1.05-1.29; P = .003). The association of severe TR with survival was dependent on estimated right ventricular (RV) pressure, with a more pronounced effect among patients with estimated systolic pressure ≤ 40 mm Hg (hazard ratio, 2.12 vs 1.04; P for interaction < .001). A landmark subanalysis of 17,967 patients demonstrated that RV function deterioration on follow-up echocardiography modified the association of severe TR with survival. It was more significant among patients with preserved and stable RV function (P for interaction = .035). CONCLUSIONS: The outcome of severe TR is modified by RV pressure and function. Once RV function deteriorates, differences in the outcomes of patients with and without severe TR are less pronounced.

Influence of anesthesia on hemodynamic assessment of mitral stenosis severity.

BACKGROUND: The treatment of choice for severe rheumatic mitral stenosis (MS) is balloon mitral valvuloplasty (BMV). Assessment of MS severity is usually performed by echocardiography. Before performing BMV, invasive hemodynamic assessment is also performed. The effect of anesthesia on the invasive assessment of MS severity has not been studied. The purpose of the present study was to assess changes in invasive hemodynamic measurement of MS severity before and after induction of general anesthesia. METHODS: The medical files of 22 patients who underwent BMV between 2014 and 2020 were reviewed. Medical history, laboratory, echocardiographic and invasive measurements were collected. Anesthesia induction was performed with etomidate or propofol. Pre-procedural echocardiographic measurements of valve area using pressure half time, and continuity correlated well with invasive measurements using the Gorlin formula. RESULTS: After induction of anesthesia the mean mitral valve gradient dropped by 2.4 mmHg (p = 0.153) and calculated mitral valve area (MVA) increased by 0.2 cm2 (p = 0.011). A wide variability in individual response was observed. While a drop in gradient was noted in 14 patients, it increased in 7. Gorlin derived MVA rose in most patients but dropped in 4. Assuming a calculated MVA of 1.5 cm2 and below to define clinically significant MS, 4 patients with pre-induction MVA of 1.5 cm2 or below had calculated MVA above 1.5 cm2 after induction. CONCLUSIONS: The impact of general anesthesia on the hemodynamic assessment of MS is heterogeneous and may lead to misclassification of MS severity.

Erythropoietin derivate improves left ventricular systolic performance and attenuates left ventricular remodeling in rats with myocardial infarct-induced heart failure.

BACKGROUND: It has been reported that erythropoietin (EPO) attenuates ischemia-induced damage in a variety of tissues. It is unknown whether EPO alters the left ventricular (LV) remodeling process after ischemic insult. Accordingly, we tested the potential benefits of carbamylated EPO (CEPO) on LV remodeling in rats with myocardial infarction (MI). METHODS: MI was induced by coronary artery ligation in adult male Sprague-Dawley rats. One hour after surgery, rats were randomly assigned to 1 of 2 groups: MI plus placebo injections (placebo, n = 21) and MI plus CEPO injection (CEPO, n = 22). CEPO (10 µg/kg) or placebo was given via tail vein in a blinded fashion daily for the first 3 days, followed by twice a week subcutaneous injection for 6 weeks. Sham surgery was performed in another group of rats (n = 18) without coronary artery ligation. Cardiac function was assessed by echocardiography, hemodynamic, and in vivo and ex vivo LV pressure-volume relationship measurements 6 weeks after MI. RESULTS: In comparison to placebo-treated rats, CEPO significantly improved LV geometry (LV end systolic dimension: 8.6 ± 0.8 vs. 9.6 ± 1.0 mm; LV end systolic volume: 404 ± 83 vs. 516 ± 122 µL, both P < 0.05). CEPO therapy also reduced the decline of systolic function (fractional shortening: -3.7% ± 1.7% vs. -10.9% ± 2.3%; Emax 0.46 ± 0.20 vs. 0.25 ± 0.08 mm Hg/s, both P < 0.05). Passive diastolic properties of the LV were minimally improved by leftward shift in the ex vivo end diastolic pressure-volume relationship. CONCLUSIONS: CEPO administration 1 hour after acute MI improves systolic performance and may attenuate the LV remodeling process. Further studies to determine the mechanism of CEPO responsible for its beneficial effects and optimize dosing and timing regimens are warranted.

Long-term effects of B-type natriuretic peptide infusion after acute myocardial infarction in a rat model.

INTRODUCTION: The effects of exogenous B-type natriuretic peptide (BNP) on postmyocardial infarction (MI) are not known. We tested the hypothesis that in vivo infusion of BNP would improve cardiac function and affect left ventricular (LV) remodeling in an experimental model of MI. METHODS: MI was induced by coronary ligation in rats and confirmed by echocardiography. 19 rats were randomized to 1 of 3 groups: sham (n = 7), MI + saline (n = 5), MI + BNP (400 ng.kg(-1).minute(-1)) (n = 7). Infusions were delivered for 7 days via venous catheters tunneled to an infusion pump. Rats were followed for 8 weeks. Echocardiography, hemodynamics, histology, and in vivo and ex vivo pressure-volume relationships were examined. RESULTS: LV systolic pressure, LV dP/dtmax, and infarct size improved with BNP treatment versus control MI group (132 +/- 4 vs.110 +/- 2 mm Hg, 8097 +/- 317 vs. 5816 +/- 378 mm Hg/s, 19.3% +/- 1.6% vs. 23.3% +/- 1.9%, respectively; all P < 0.05). Ex vivo end-diastolic pressure-volume relationship demonstrated reduced diastolic dysfunction after BNP therapy (P < 0.05 vs. control MI). Serum BNP levels confirmed delivery of BNP. CONCLUSIONS: We demonstrate beneficial effects on LV function and decreased LV remodeling with BNP infusion in an experimental model of acute MI.

The prognostic significance of improvement in exercise capacity in heart failure patients who participate in cardiac rehabilitation programme.

Introduction There are limited contemporary data regarding the association between improvement in cardiovascular fitness in heart failure patients who participate in a cardiac rehabilitation programme and the risk of subsequent hospitalisations. Methods The study population comprised 421 patients with heart failure who participated in our cardiac rehabilitation programme between the years 2009 and 2016. All were evaluated by a standard exercise stress test before initiation, and underwent a second exercise stress test on completion of 3 ± 1 months of training. Participants were dichotomised by fitness level at baseline, according to the percentage of predicted age and sex norms achieved. Each group was further divided according to its degree of functional improvement, between the baseline and the follow-up exercise stress test. Major improvement was defined as improvement above the median value in each group. The combined primary endpoint was cardiac hospitalisation or all-cause mortality. Results A total of 211 (50%) patients had low baseline fitness (<73% (median)) for age and sex-predicted metabolic equivalents of task value. Compared to patients with higher fitness, those with a low baseline fitness were more commonly smokers, had diabetes and were obese ( P < 0.05 for all). Multivariable Cox proportional hazard regression analysis showed that, independent of baseline capacity, an improvement of 5% of predicted fitness was associated with a corresponding 10% reduced risk of cardiac hospitalisation or all-cause mortality ( P < 0.001). Conclusion In heart failure patients participating in a cardiac rehabilitation programme, improved cardiovascular fitness is associated with reduced mortality or cardiac hospitalisation risk during long-term follow-up, independent of baseline fitness.

Cardiac CT Angiography (CCTA) predicts left atrial appendage occluder device size and procedure outcome.

AIM: To investigate the role of cardiac CT angiography (CCTA) in predicting optimal left atrial appendage (LAA) occluder size and procedure outcome. METHODS AND RESULTS: Thirty-six patients underwent pre-procedural CCTA. CCTA and TEE LAA orifice diameters and perimeters were compared with the implanted device size. CCTA 3D configuration was correlated with procedure outcome. Watchman™ device (N = 18): diameters were 21 ± 4, 26 ± 5 and 25 ± 3 mm for TEE, CCTA and inserted device, respectively. Average perimeters were 61 ± 10, 74 ± 8 and 78 ± 11 mm for TEE, CCTA and inserted device, respectively. Better agreement with the device size was found for CCTA compared to TEE (Bland-Altman). ACP™ device (N = 15): diameters were 20 ± 5, 25 ± 4 and 23 ± 4 for TEE, CCTA and inserted device, respectively. Average perimeters were 58 ± 11, 72 ± 15 and 72 ± 13 mm for TEE, CCTA and inserted device, respectively. Excellent correlation and agreement with the device size was found for CCTA compared to TEE. CCTA perimeter >100 mm and "cactus" 3D configuration had a specificity of 96 and 81% respectively for procedure failure. CONCLUSIONS: CCTA LAA ostial perimeter predicted better the optimal occluder size as compared with the currently used LAA TEE diameter. Moreover, CCTA 3D data may help in predicting potential complications.

The benefit of upgrading chronically right ventricle-paced heart failure patients to resynchronization therapy demonstrated by strain rate imaging.

BACKGROUND: RV pacing induces conduction delay (CD), mechanical dyssynchrony, and increased morbidity in patients with HF. CRT improves HF symptoms and survival, but sparse data exist on its direct effect on chronically RV-paced HF patients. OBJECTIVES: To assess the benefit of cardiac resynchronization therapy (CRT) in chronically right ventricle (RV)-paced heart failure (HF) patients. METHODS: We studied 12 consecutive patients with class III HF who had a previously implanted pacemaker or implantable cardioverter-defibrillator. These individuals were chronically RV paced and referred for upgrade to a biventricular device by their primary cardiologists. Tissue Doppler and strain rate imaging (TDI and SRI, respectively) were performed immediately before each upgrade and 4-6 weeks afterward to quantify changes in regional wall motion and synchrony with CRT. RESULTS: CRT significantly reduced the mean QRS duration (205 ms to 156 ms; P<.0001), and it increased the ejection fraction (30.7%+/-5.1% to 35.8%+/-5.1%; P<.01). Left ventricular end-systolic and end-diastolic dimensions were also significantly reduced. Clinically, patients improved by an average of one New York Heart Association (NYHA) functional class after upgrade (P = .006). The parameter exhibiting greatest improvement was the coefficient of variation (CoV: standard deviation/mean) of time to peak systolic strain rate, a marker of ventricular dyssynchrony, which decreased from 34.3%+/-13.0% to 19.0%+/-6.6% (P<.01). Reduction in CoV of time to peak systolic strain rate was maximally seen in the midventricle (38.2%+/-19.6% to 16.5%+/-9.7%; P<.01). CONCLUSIONS: Upgrading chronically RV-paced HF patients to CRT improves global and regional systolic function. TDI and SRI provide compelling evidence that this benefit parallels that seen in HF patients with CD unrelated to RV pacing, which implies that biventricular pacing synchronizes mechanical activation in different myocardial regions in patients upgraded from RV pacing as well.

Combined ventricular systolic and arterial stiffening in patients with heart failure and preserved ejection fraction: implications for systolic and diastolic reserve limitations.

BACKGROUND: Heart failure with preserved ejection fraction (HF-nlEF) is common in aged individuals with systolic hypertension and is frequently ascribed to diastolic dysfunction. We hypothesized that such patients also display combined ventricular-systolic and arterial stiffening that can exacerbate blood pressure lability and diastolic dysfunction under stress. METHODS AND RESULTS: Left ventricular pressure-volume relations were measured in patients with HF-nlEF (n=10) and contrasted with asymptomatic age-matched (n=9) and young (n=14) normotensives and age- and blood pressure-matched controls (n=25). End-systolic elastance (stiffness) was higher in patients with HF-nlEF (4.7+/-1.5 mm Hg/mL) than in controls (2.1+/-0.9 mm Hg/mL for normotensives and 3.3+/-1.0 mm Hg/mL for hypertensives; P<0.001). Effective arterial elastance was also higher (2.6+/-0.5 versus 1.9+/-0.5 mm Hg/mL) due to reduced total arterial compliance; the latter inversely correlated with end-systolic elastance (P=0.0001). Body size and stroke volumes were similar and could not explain differences in ventricular-arterial stiffening. HF-nlEF patients also displayed diastolic abnormalities, including higher left ventricular end-diastolic pressures (24.3+/-4.6 versus 12.9+/-5.5 mm Hg), caused by an upward-shifted diastolic pressure-volume curve. However, isovolumic relaxation and the early-to-late filling ratio were similar in age- and blood pressure-matched controls. Ventricular-arterial stiffening amplified stress-induced hypertension, which worsened diastolic function, and predicted higher cardiac energy costs to provide reserve output. CONCLUSION: Patients with HF-lnEF have systolic-ventricular and arterial stiffening beyond that associated with aging and/or hypertension. This may play an important pathophysiological role by exacerbating systemic load interaction with diastolic function, augmenting blood pressure lability, and elevating cardiac metabolic demand under stress.

Short-term effects of right-left heart sequential cardiac resynchronization in patients with heart failure, chronic atrial fibrillation, and atrioventricular nodal block.

BACKGROUND: Single-site ventricular pacing in patients with heart failure, atrial fibrillation, and severe atrioventricular (AV) nodal block risks the generation of discoordinate contraction. Whether altering the site of stimulation can offset this detrimental effect and what role sequential right ventricular-left ventricular (RV-LV) stimulation might play in such patients remain unknown. METHODS AND RESULTS: Nine subjects with heart failure (ejection fraction, 14% to 30%), atrial fibrillation, and AV block were studied by pressure-volume analysis. Ventricular stimulation was applied to the RV (apex and outflow tract), LV free wall, and biventricular (BiV) at 80 and 120 bpm. BiV improved systolic function more than either site alone (dP/dt(max), 810+/-83, 924+/-98, 983+/-102 mm Hg/s for RV, LV, BiV, respectively; P<0.05), although LV pacing was significantly better than RV pacing. However, only BiV improved diastolic function (isovolumic relaxation) over RV or LV alone. Similar results were obtained for both heart rates. RV pacing site did not alter the BiV effect, and concomitant stimulation of both RV sites did not improve function over each alone. Finally, varying RV-LV delay revealed optimal responses with simultaneous pacing. CONCLUSIONS: Simultaneous BiV pacing acutely enhances both systolic and diastolic function over single-site RV or LV pacing in congestive heart failure patients with atrial fibrillation and advanced AV block. Sequential RV-LV stimulation offers minimal benefit on average and should perhaps be considered only in targeted subsets such as nonresponding patients.

Efficacy of exercise training in symptomatic patients with hypertrophic cardiomyopathy: results of a structured exercise training program in a cardiac rehabilitation center.

BACKGROUND: Recent data suggest that exercise training (ET) confers significant symptomatic and functional improvements in patients with diastolic dysfunction, and thus may be beneficial in patients with hypertrophic cardiomyopathy (HCM). However, there are no data regarding the safety or efficacy of ET in HCM patients. DESIGN: A prospective non-randomized intervention design was used. METHODS: We enrolled 20 patients with symptomatic HCM, significantly limited in everyday activity, into a supervised cardiac rehabilitation exercise program. RESULTS: Patients were 62 ± 13 years old, in New York Heart Association (NYHA) functional class II (35%) or III (65%), had a mean interventricular septum dimension of 17 ± 5 mm and left ventricular ejection fraction (LVEF) of 53 ± 15%. Left ventricular outflow gradient was present at rest in nine patients (mean 51 ± 24 mm Hg) and six patients had an implantable defibrillator. Exercise prescription was based on heart rate reserve (HRR) determined from a symptom-limited graded exercise stress test. Exercise intensity was gradually increased from 50% to 85% of the HRR over the training period. Patients completed an average of 41 ± 8 hours of aerobic ET. No adverse events or sustained ventricular arrhythmias occurred during the training program. Functional capacity, assessed by a graded exercise test, improved from 4.7 ± 2.2 to 7.2 ± 2.8 metabolic equivalents (METs) (p = 0.01). NYHA functional class improved from baseline by ≥ 1 grade in 10 patients (50%) and none experiencing deterioration during follow-up. CONCLUSIONS: The present study suggests that patients with HCM who remain symptomatic despite medical therapy may achieve considerable functional improvement through a supervised ET program.

The significance of pulmonary arterial hypertension pre- and post-transfemoral aortic valve implantation for severe aortic stenosis.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) has become the treatment of choice for the symptomatic patients with aortic stenosis (AS) and high surgical risk. Pulmonary hypertension (PHTN) has been shown to be associated with worse early and late outcomes after aortic valve surgery. Data regarding the effect of TAVI on PHTN are limited. METHODS AND RESULTS: We evaluated the characteristics and outcome of the patients with various degrees of systolic PHTN referred for TAVI. PHTN was defined as systolic pulmonary arterial pressure (SPAP) ≥50mmHg as assessed by echocardiography. The patients with SPAP decrease after TAVI to below 50mmHg were compared to the patients with persistent PHTN following TAVI. Of the 122 patients included in the present study, 49 (40%) patients had elevated SPAP prior to TAVI. This group of patients presented with smaller aortic valve areas, greater degrees of mitral or tricuspid regurgitation, lower left ventricular ejection fraction, and more prevalent chronic obstructive pulmonary disease (COPD) (all p<0.05). Following TAVI, 57% of the patients with prior PHTN experienced a reduction in SPAP to below 50mmHg. Multivariable analysis identified COPD to be the most powerful predictor for PHTN presence post-TAVI (hazard ratio 3.9, 95% confidence interval 1.5-9.9, p=0.005). Post-TAVI PHTN (SPAP ≥50mmHg) was associated with a 3.4-fold, independent, 2-year mortality risk (p=0.04). CONCLUSIONS: Our data suggest that TAVI is associated with a significant reduction in pulmonary pressure in more than half of the patients with preprocedural PHTN. COPD identifies the patients with persistent PHTN after TAVI. Post-TAVI PHTN is associated with markedly worse outcome.

Deformation dynamics and mechanical properties of the aortic annulus by 4-dimensional computed tomography: insights into the functional anatomy of the aortic valve complex and implications for transcatheter aortic valve therapy.

OBJECTIVES: The purpose of this study was to assess deformation dynamics and in vivo mechanical properties of the aortic annulus throughout the cardiac cycle. BACKGROUND: Understanding dynamic aspects of functional aortic valve anatomy is important for beating-heart transcatheter aortic valve implantation. METHODS: Thirty-five patients with aortic stenosis and 11 normal subjects underwent 256-slice computed tomography. The aortic annulus plane was reconstructed in 10% increments over the cardiac cycle. For each phase, minimum diameter, ellipticity index, cross-sectional area (CSA), and perimeter (Perim) were measured. In a subset of 10 patients, Young's elastic module was calculated from the stress-strain relationship of the annulus. RESULTS: In both subjects with normal and with calcified aortic valves, minimum diameter increased in systole (12.3 ± 7.3% and 9.8 ± 3.4%, respectively; p < 0.001), and ellipticity index decreased (12.7 ± 8.8% and 10.3 ± 2.7%, respectively; p < 0.001). The CSA increased by 11.2 ± 5.4% and 6.2 ± 4.8%, respectively (p < 0.001). Perim increase was negligible in patients with calcified valves (0.56 ± 0.85%; p < 0.001) and small even in normal subjects (2.2 ± 2.2%; p = 0.01). Accordingly, relative percentage differences between maximum and minimum values were significantly smallest for Perim compared with all other parameters. Young's modulus was calculated as 22.6 ± 9.2 MPa in patients and 13.8 ± 6.4 MPa in normal subjects. CONCLUSIONS: The aortic annulus, generally elliptic, assumes a more round shape in systole, thus increasing CSA without substantial change in perimeter. Perimeter changes are negligible in patients with calcified valves, because tissue properties allow very little expansion. Aortic annulus perimeter appears therefore ideally suited for accurate sizing in transcatheter aortic valve implantation.