Implications of Indeterminate and Determined Etiologies Leading to Small Left Atria.

BACKGROUND: Small left atria (LA) is associated with an increased risk of mortality. OBJECTIVES: To determine whether the attributed risk of mortality is influenced by the underlying etiologies leading to decreased volumes. METHODS: We retrospectively evaluated patients with an available LA volume index (LAVI) as measured by echocardiography who came to our institution between 2011 and 2016. Individuals with small LA (LAVI < 16 ml/m2) were included and divided according to the etiology of the small LA (determined or indeterminate) and investigated according to the specific etiology. RESULTS: The cohort consisted of 288 patients with a mean age of 56 ± 18 years. An etiology for small LA was determined in 84% (n=242). The 1-year mortality rate of the entire cohort was 20.5%. Patients with indeterminate etiology (n=46) demonstrated a lower mortality rate compared with determined etiologies (8.7% vs. 22.7%, P = 0.031). However, following propensity score adjustments for baseline characteristics, there was no significant difference between the groups (P = 0.149). The only specific etiology independently associated with 1-year mortality was the presence of space occupying lesions (odds ratio 3.26, 95% confidence interval 1.02-10.39, P = 0.045). CONCLUSIONS: Small LA serve as a marker for negative outcomes, and even in cases of undetected etiology, the prognosis remains poor. The presence of small LA should alert the physician to a high risk of mortality, regardless of the underlying disease.

Re-Appraisal of Echocardiographic Assessment in Patients with Pulmonary Embolism: Prospective Blinded Long-Term Follow-Up.

BACKGROUND: Acute pulmonary embolism (PE) is considered to be one of the most common cardiovascular diseases with considerable mortality. Conflicting data imply possible role for echocardiography in assessing this disease. OBJECTIVES: To determine which of the echo parameters best predicts short-term and long-term mortality in patients with PE. METHODS: We prospectively enrolled 235 patients who underwent computed tomography of pulmonary arteries (CTPA) and transthoracic Echocardiography (TTE) within < 24 hours. TTE included a prospectively designed detailed evaluation of the right heart including right ventricular (RV) myocardial performance index (RIMP), RV end diastolic and end systolic area, RV fractional area change, acceleration time (AT) of pulmonary flow and visual estimation. Interpretation and performance of TTE were blinded to the CTPA results. RESULTS: Although multiple TTE parameters were associated with PE, all had low discriminative capacity (AUC < 0.7). Parameters associated with 30-day mortality in univariate analysis were acceleration time (AT) < 81 msec (P = 0.04), stroke volume < 44 cc (P = 0.005), and RIMP > 0.42 (P = 0.05). The only RV independent echo parameter associated with poor long-term prognosis (adjusted for significant clinical, and routine echo associates of mortality) was RIMP (hazard ratio 3.0, P = 0.04). The only independent RV echo parameters associated with mortality in PE patients were RIMP (P = 0.05) and AT (P = 0.05). Addition of RIMP to nested models eliminated the significance of all other parameters assessing RV function. CONCLUSIONS: Doppler-based parameters like pulmonary flow AT, RIMP, and stroke volume, have additive value in addition to visual RV estimation to assess prognosis in patients with PE.

Conduction Abnormalities after Transcatheter Aortic Valve Implantation and Diastolic Dysfunction.

OBJECTIVES: Transcatheter aortic valve implantation (TAVI) is frequently associated with the development of conduction abnormalities. We assessed the effect of conduction abnormalities on diastolic function following TAVI. METHODS: In total, 101 consecutive post-TAVI patients were included, each with echocardiographic follow-up at 1 and 6 months. Diastolic properties were correlated with the occurrence of a long PR interval and wide QRS, and their change from baseline. The measured diastolic parameters included E/A ratio, E wave deceleration time, E wave to e' ratio, left atrial (LA) volume, and systolic pulmonary artery pressure (SPAP). The clinical outcome was all-cause mortality. RESULTS: Overall, TAVI was associated with a consistent decrease in SPAP at the 1- and 6-month follow-up. LA volumes were increased at 1 month post-TAVI in patients with a wide compared to normal QRS (p = 0.03) and at 6 months in patients with a normal compared to prolonged PR (p = 0.03). PR prolongation above 40 ms was associated with lower SPAP at the 1- but not 6-month follow-up. Survival was not influenced by conduction abnormalities. CONCLUSIONS: TAVI is associated with a reduction in SPAP. A postprocedural wide QRS and normal PR interval may unfavorably influence the left-sided filling performance, resulting in an increased LA volume. Other diastolic parameters, as well as survival, are not significantly affected by postprocedural conduction abnormalities.

Aortic regurgitation following transcatheter aortic valve replacement: Impact of preprocedural left ventricular diastolic filling patterns on late clinical outcomes.

OBJECTIVES: To investigate the impact of preprocedural left ventricular (LV) diastolic function on outcomes of patients with postprocedural aortic regurgitation (ARpost ) following transcatheter aortic valve replacement (TAVR). BACKGROUND: The predictors and mechanisms of the increased mortality in patients with ARpost are inadequately defined. METHODS: Baseline clinical and echocardiographic variables from a prospective TAVR registry were analyzed. Preprocedural correlates of late outcomes (all-cause mortality and the composite of mortality, stroke, heart failure, and new-onset atrial fibrillation) were examined according to the presence and severity of ARpost . RESULTS: Of the 418 patients undergoing TAVR, ARpost was present in 212 (51%): mild 36%, moderate-severe 15%. Mean follow-up was 909 ± 489 days. All-cause mortality and composite endpoint rates were significantly increased in patients with moderate-severe ARpost compared with patients with either none or only mild ARpost (38, 22, 21%, P = 0.02; and, 56, 35, 40%, P = 0.01; respectively). Moderate-severe (though not mild) ARpost was independently associated with mortality and the composite endpoint (HR = 1.93 [95%CI 1.15-3.14], P = 0.01; HR = 1.85 [95%CI 1.22-2.77], P = 0.004], respectively). By multivariate analysis, preprocedural LV deceleration time (DT) < 160 ms was independently associated with the risk of all-cause mortality and the composite endpoint among patients with mild AR (HR = 1.74 [95%CI 1.14-2.60], P = 0.01; and, HR = 1.73 [95%CI 1.23-2.41], P = 0.002, respectively) and moderate-severe ARpost (HR = 1.81 [95%CI 1.28-2.51], P < 0.001; HR = 1.86 [95%CI 0.22-2.80], P = 0.004, respectively). CONCLUSIONS: Preprocedural impairment of LV filling, reflected by short DT, portends an adverse prognosis in TAVR patients who develop ARpost independently of other clinical and echocardiocardigraphic measures including AS severity and systolic LV function. © 2015 Wiley Periodicals, Inc.

Echo Doppler Estimation of Pulmonary Capillary Wedge Pressure in Patients with Severe Aortic Stenosis.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has become a treatment option for patients with severe aortic stenosis (AS) and high surgical risk. Assessment of symptoms in these patients is challenging because of advanced age, comorbidities, and limited physical activity. Noninvasive quantification of pulmonary capillary wedge pressure (PCWP) in candidates for TAVR may be helpful for risk stratification. The objective of the study was to create a model for estimation of PCWP by echo Doppler in patients with severe AS. METHODS AND RESULTS: Data from 80 patients with severe AS referred for TAVR were used to develop an echo Doppler model for predicting PCWP. Its performance was evaluated in the test cohort of 33 patients who had invasive and noninvasive evaluation. No single echo Doppler parameter estimated PCWP accurately. In the retrospective analysis, the multilinear regression provided an accurate estimate of PCWP (r(2) = 0.74). The model included, in order of importance (all P < 0.05), the ratio of early transmitral velocity (E) to annular velocity (E'), the left ventricular ejection fraction, and the velocity time integral of tricuspid regurgitation signal. In the prospective cohort of patients with severe AS, the model demonstrated good predictive ability of PCWP (r = 0.77, P < 0.01). CONCLUSION: In patients with severe AS, noninvasive estimation of PCWP is possible by integration of two-dimensional, spectral, and tissue Doppler variables.

Long-term clinical and echocardiographic follow-up of the freestyle stentless aortic bioprosthesis: the Tel Aviv Medical Center experience.

BACKGROUND: Stentless aortic bioprostheses were designed to provide improved hemodynamic performance and potentially better survival. OBJECTIVES: To report the outcomes of patients after aortic valve replacement with the Freestyle stentless bioprosthesis at the Tel Aviv Medical Center followed for < or = 15 years. METHODS AND RESULTS: Between 1997 and 2011, 268 patients underwent primary aortic valve replacement with a Freestyle bioprosthesis, 211 (79%) of them in the sub-coronary position. Mean age, Charlson comorbidity index and Euro-score were 71.0 +/- 9.2 years, 4.2 +/- 1.5 and 10.2 +/- 11 respectively, and 156 (58%) were male. Peak and mean trans-aortic gradient decreased significantly (75.0 +/- 29.1 vs. 22.8 +/- 9.6 mmHg, P < 0.0001; and 43.4 +/- 17.2 vs. 12.1 +/- 5.4 mmHg, P < 0.0001 respectively) during 3 months of follow-up. Mean overall follow-up was 4.9 +/- 3.1 years and was complete in all patients. In-hospital mortality was 4.1% (n=11) but differed significantly between the first 100 patients operated before 2006 and the last 168 patients operated after January 2006 (8 vs. 3 patients, 8.0% vs. 1.8%, P = 0.01). Overall, 5 and 10 year survival rates were 85 +/- 2.5% and 57.2 +/- 5.7%, respectively. Five year survival was markedly improved in patients operated after January 2006 compared to those operated in the early years of the experience (92.3 +/- 2.3% vs. 76.0 +/- 4.4%, P = 0.0009). All the 21 octogenarians operated after January 2006 survived surgery, with excellent 5 year survival (85.1 +/- 7.9%). Six patients required reoperation during follow-up: structural valve deterioration in five and endocarditis in one. CONCLUSIONS: Aortic valve replacement with the Freestyle bioprosthesis provides good long-term hemodynamic and clinical outcomes, even in octogenarians. Valve calcification is the major (and rare) mode of valve deterioration leading to reoperation in these patients.

Transcatheter aortic valve implantation: a single-center experience of 300 cases.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) has recently become an alternative to surgical aortic valve replacement in selected patients with high operative risk. OBJECTIVES: To investigate the 30 day clinical outcome of the first 300 consecutive patients treated with transfemoral TAVI at the Tel Aviv Medical Center. METHODS: The CoreValve was used in 250 patients and the Edwards-Sapien valve in 50. The mean age of the patients was 83 +/- 5.3 years (range 63-98 years) and the mean valve area 0.69 +/- 0.18 cm2 (range 0.3-0.9 cm2); 62% were women. RESULTS: The procedural success rate was 100%, and 30 day follow-up was done in all the patients. The average Euro-score for the cohort was 26 +/- 13 (range 1.5-67). Total in-hospital mortality and 30 day mortality were both 2.3% (7 patients). Sixty-seven patients (22%) underwent permanent pacemaker implantation after the TAVI procedure, mostly due to new onset of left bundle brunch block and prolonged PR interval or to high degree atrioventricular block. The rate of stroke was 1.7% (5 patients). Forty-one patients (13.7%) had vascular complications, of whom 9 (3%) were defined as major vascular complications (according to the VARC definition). CONCLUSIONS: The 30 day clinical outcome in the first 300 consecutive TAVI patients in our center was favorable, with a mortality rate of 2.3% and low rates of stroke (1.7%) and major vascular complications (3%).

Clinical impact of post procedural mitral regurgitation after transcatheter aortic valve replacement.

BACKGROUND: While the impact of mitral regurgitation (MR) prior to transcatheter aortic valve replacement (TAVR) has been intensively studied, the implications of post-procedural MR on outcome are unknown. We investigated the clinical and physiological impact of significant MR after TAVR. METHODS: Clinical and echocardiographic data of 486 patients who underwent TAVR between March 2009 and December 2014 were evaluated. Clinical endpoints included overall mortality and combined endpoint of mortality, heart failure re-hospitalization and new atrial fibrillation. Echocardiographic parameters were analyzed at baseline, 30-day and 6-month after TAVR. RESULTS: MR severity improved in 25%, worsened in 19% and did not change in 56% of patients 30-days post TAVR (p = 0.3). Post TAVR MR grade ≥ moderate was present in 16.1%. Predictive accuracy of post TAVR MR was low (AUC = 0.63). Median follow-up was 4.3 years (interquartile range, 2.5 to 6.1). Post TAVR MR grade ≥ moderate was associated with increased mortality and combined cardiac events (p = 0.013 and p < 0.001) even when adjusted for all clinical and echo parameters and when analyzed with propensity score matching. In patients with MR ≥ moderate, LV filling pressure and RV hemodynamics worsened 6 months post TAVR, while improving in patients with less significant post procedural MR. CONCLUSION: Post procedural, but not pre-procedural MR grade ≥ moderate was independently associated with mortality and adverse cardiac events after TAVR. Significant MR post TAVR resulted in adverse LV and RV remodeling and poor hemodynamic. Our study strengthens the rational for initiating early treatment to reduce post TAVR MR.

Quantitative assessment of effective regurgitant orifice: impact on risk stratification, and cut-off for severe and torrential tricuspid regurgitation grade.

AIMS: Asses the added value of quantitative evaluation of tricuspid regurgitation (TR), the proper cut-off value for severe TR and 'torrential TR' based on outcome data. The added value of quantitative evaluation of TR, and the cut-off values associated with increased mortality are unknown. METHODS AND RESULTS: In patients with all-cause TR assessed both qualitatively and quantitatively by proximal iso-velocity surface area method, long-term and 1-year outcome analysis was conducted. Thresholds for excess mortality were assessed using spline curves, receiver-operating characteristic curves, and minimum P-value analysis. The study involved 676 patients with all-cause TR (age 73.9 ± 14 years, male 45%, ejection fraction 52.9 ± 14%). Effective regurgitant orifice (ERO) was strongly associated with decreased survival in unadjusted [hazard ratio (HR) 2.38 (1.79-3.01), P < 0.0001 per 0.1 cm2 increment] and adjusted [2.6 (1.25-5.0), P = 0.01] analyses. Quantitative grading was superior to qualitative grading in prediction of outcome (P < 0.01). The optimal cut-off value for the best separation in survival between groups of patients with severe vs. lesser degree of TR was 0.35 cm2 [P < 0.0001, HR =2.0 (1.5-2.7)]. ERO negatively impacted survival, even when including only the subgroup of patients with severe TR [HR 1.5 (1.01-2.3); P = 0.04]. The optimal threshold corresponding for the best separation for survival between groups of patients with severe vs. 'torrential' TR was 0.7 cm2 [P = 0.005, HR =2.6 (1.2-5.1)]. CONCLUSION: TR can be severe and even 'torrential' and is associated with excess mortality. Quantitative assessment of TR by ERO measurement is a powerful independent predictor of outcome, superior to standard qualitative assessment. The optimal cut-off above which mortality is increased is 0.35 cm2, similar albeit slightly lower than suggested in recent guidelines. Torrential TR >0.7 cm2 is associated with poorer survival compared to patients with severe TR (ERO > 0.4 cm2 and <0.7 cm2).

Visual assessment of left ventricular dyssynchrony using tissue synchronization imaging.

BACKGROUND: Tissue synchronizing imaging (TSI) allows visual detection of asynchronous myocardial contraction. Although it is a screening tool for the detection of left ventricular (LV) dyssynchrony, its use as a qualitative method to assess dyssynchrony has not been studied. We evaluated the correlation of the visual assessment of dyssynchrony using TSI with quantitative assessment, the value of visual assessment to predict reverse remodeling to cardiac resynchronization therapy (CRT). METHODS: Echocardiograms from 100 consecutive patients were retrospectively evaluated. We compared visual TSI assessment with the qualitative assessment of dyssynchrony obtained by tissue Doppler imaging (TDI). The utility of visual assessment as a predictor of response to CRT was evaluated in 43 patients. RESULTS: In 86% of the cases, visual assessment was possible, and reproducibility was unrelated to observer experience. Each grade of visual dyssynchrony corresponded to a range of values of time to peak velocity (TPV) gradient (p < 0.001). Grade >or=1 dyssynchrony by visual assessment had 90% sensitivity and 95% specificity to identify >or=65 ms TPV gradient of LV opposing walls, and 93% sensitivity and 70% specificity to predict reverse LV remodeling. CONCLUSION: LV dyssynchrony may be visually assessed by TSI, which can also predict reverse LV remodeling.

Prognostic Implications of Baseline Pulmonary Vascular Resistance Determined by Transthoracic Echocardiography Before Transcatheter Aortic Valve Replacement.

BACKGROUND: Elevated pulmonary vascular resistance (PVR) determined using right heart catheterization portends an adverse prognosis following transcatheter aortic valve replacement (TAVR). The prognostic role of preprocedural PVR determined noninvasively using transthoracic echocardiography has not been studied in the TAVR setting. METHODS: Baseline clinical and echocardiographic variables from a prospective TAVR registry were analyzed to determine preprocedural PVR and its impact on late outcomes (all-cause mortality, stroke, readmission for heart failure, new-onset atrial fibrillation). Echocardiographic PVR was estimated by the ratio of peak tricuspid regurgitation velocity to the time-velocity integral of the right ventricular outflow tract. RESULTS: Ninety-seven patients were included in the study, with complete 3-year follow-up data available for all survivors. Mean PVR was 2.1 ± 0.) WU in the entire cohort and 2.7 ± 0.9 WU among patients with pulmonary hypertension. In the entire cohort, 29 patients (29.9%) died during the study period. Three-year all-cause mortality and composite adverse event rates were higher with increased versus normal PVR (55.6% vs 24.1% [P = .008] and 66.7% vs 41.8% [P = .06], respectively). By multivariate analysis, PVR as either a continuous (hazard ratio, 1.75; 95% CI, 1.1-2.81; P = .02) or a categorical (≥2.5 vs >2.5 WU; hazard ratio, 2.49; 95% CI, 1.09-5.71; P = .03) variable was independently associated with all-cause mortality. Although systolic pulmonary artery pressure was associated with all-cause mortality on univariate analysis, this association was not statistically significant on multivariate analysis accounting for PVR. CONCLUSIONS: PVR estimated using transthoracic echocardiography is an independent predictor of mortality at long-term follow-up after TAVR. Systolic pulmonary artery pressure was associated with increased late mortality, although this relation was not significant after adjustment for baseline variables and PVR.

Prognostic implications of small left atria on hospitalized patients.

AIMS: To demonstrate the association between small left atria (LA) and outcome in a relatively large heterogeneous population of hospitalized patients. METHODS AND RESULTS: In a single-centre retrospective study, all inpatients that underwent an echocardiographic assessment between 2011 and 2016 and had an available left atrial volume index (LAVI) measurement were included. The cohort consisted of 17 343 inpatients who had an available LAVI measurement, 288 with small LA (LAVI <16 mL/m2), 7531 patients had LAVI within normal limits (16-34 mL/m2) divided into low normal (16-24.9 mL/m2; n = 2636) and high normal (25-34 mL/m2; n = 4895), 4720 patients had large LAVI (34.1-45 mL/m2) and 4804 had very large LAVI (>45 mL/m2). Median follow-up time was 2.4 years. After adjustments for age, gender, and baseline characteristics with a P-value <0.2 in univariable analyses (body mass index, haemoglobin, ischaemic heart disease, valvulopathy, atrial fibrillation, diabetes mellitus, hypertension, hyperlipidaemia, smoking, renal dysfunction, lung disease, and malignancy) small LA was associated with a higher risk for in-hospital mortality (odds ratio 2.9, 95% confidence interval (CI) 1.4-5.7; P = 0.002] and all-cause mortality [hazard ratio (HR) 2.1, 95% CI 1.6-2.8; P < 0.001] compared with high normal LA. For every mL/m2 decrease below high normal LA size the risk for in-hospital and long-term all-cause mortality increased by 10% (HR 1.1, 95% CI 1.02-1.18; P = 0.005) and 8% (HR 1.08, 95% CI 1.05-1.12; P < 0.001), respectively. CONCLUSION: Small LA are independently associated poorer short- and long-term mortality. LA volume should be referred to as J-shaped in terms of mortality. HELSINKI COMMITTEE APPROVAL NUMBER: 0170-17-TLV.

Impact of right ventricular dysfunction and end-diastolic pulmonary artery pressure estimated from analysis of tricuspid regurgitant velocity spectrum in patients with preserved ejection fraction.

AIMS: We aimed to analyse the association between right haemodynamic parameters, right ventricular (RV) dysfunction parameters, and outcomes in patients with preserved ejection fraction (EF). METHODS AND RESULTS: Retrospective analysis of right haemodynamic (systolic pulmonary pressure and end-diastolic pulmonary pressure based on tricuspid regurgitation (TR) velocity at pulmonary valve opening time), and RV parameters including size (end-diastolic and end-systolic area), function (RV fractional area change, Tei index, Tricuspid Annular Plane Systolic Excursion, and speckle tracking derived free wall strain), from 557 consecutive patients with preserved EF [EF ≥ 50%; age 64.9 + 20; 52% female; co-morbidity Charlson index 4.7 (2.9, 6.4)]. All cause and cardiac mortality were retrospectively analysed and correlated to echo haemodynamic and co-morbid parameters. TR velocity at pulmonary valve opening time and calculated end-diastolic pulmonary artery pressure were obtainable in 71% of patients. The best haemodynamic univariate predictor of mortality was calculated end-diastolic pulmonary artery pressure [hazard ratio 1.06 (1.04-1.07); P < 0.0001], superior to TR peak velocity and systolic pulmonary artery pressure. Elevated end-diastolic pulmonary artery pressure was associated with all cause and cardiac mortality even when adjusted for all significant clinical (age, gender, and Charlson index), and echo (stroke volume index, left atrial volume index, systolic pulmonary pressure, E/e', and Tei index) parameters. Tei index was superior to all other RV functional parameters (P < 0.05 for all parameters). CONCLUSION: TR velocity at pulmonary valve opening time and calculated end-diastolic pulmonary artery pressure are obtainable in most patients, and add prognostic information on top of clinical and routine haemodynamic and diastolic parameters.

Clinical Outcome of Isolated Tricuspid Regurgitation in Patients with Preserved Left Ventricular Ejection Fraction and Pulmonary Hypertension.

BACKGROUND: The outcome of tricuspid regurgitation (TR) remains unclear because of heterogeneity of etiology and the contradictory results of outcome studies. The aim of this study was to evaluate the clinical outcomes of TR in patients with pulmonary hypertension (PH) and normal left systolic function, stratified to patients with post- or precapillary PH. METHODS: In patients with no left valvar disease (isolated) functional TR, preserved left systolic function (ejection fraction ≥ 50%), and PH (systolic pulmonary pressure > 50 mm Hg), TR was assessed both qualitatively (grade) and semiquantitatively using the vena contracta method, and retrospective analysis of long-term outcomes was conducted. Patients with severe comorbid diseases were excluded. RESULTS: The study included 245 patients (age 80.5 years, 37% men, ejection fraction 57%, all with pulmonary systolic pressure > 50 mm Hg). At least moderate to severe TR was diagnosed in 178 patients, and their outcomes were compared with those of 67 patients with the same characteristics and less than mild TR. At least moderate to severe TR was associated with lower survival, independent of all characteristics, right ventricular size or function, comorbidity, or pulmonary pressure (P = .03 for grade and P = .02 for vena contracta). Cox proportional-hazard analysis with interaction terms for TR severity and etiology of PH (post- vs precapillary) showed that the etiology of PH did not affect the association of TR with outcome (P = .90 for the interaction term). CONCLUSIONS: At least moderate to severe isolated TR is independently associated with excess mortality in patients with preserved systolic function and PH, warranting heightened attention to diagnosis and grading. This is irrespective of etiology (pre- or postcapillary) of PH. Semiquantitative assessment of TR by vena contracta is an independent associate of outcome, superior to standard qualitative assessment.

Calcium channel blockers and beta-blockers versus beta-blockers alone for preventing exercise-induced arrhythmias in catecholaminergic polymorphic ventricular tachycardia.

BACKGROUND: The mainstay of therapy for catecholaminergic polymorphic ventricular tachycardia (CPVT) is maximal doses of beta-blockers. However, although beta-blockers prevent exercise-induced ventricular tachycardia (VT), most patients continue to have ventricular ectopy during exercise, and some studies report high mortality rates despite beta-blockade. OBJECTIVE: The purpose of this study was to investigate whether combining a calcium channel blocker with beta-blockers would prevent ventricular arrhythmias during exercise better than beta-blockers alone since the mutations causing CPVT lead to intracellular calcium overload. METHODS: Five patients with CPVT and one with polymorphic VT (PVT) and hypertrophic cardiomyopathy who had exercise-induced ventricular ectopy despite beta-blocker therapy were studied. Symptom-limited exercise was first performed during maximal beta-blocker therapy and repeated after addition of oral verapamil. RESULTS: When comparing exercise during beta-blockers with exercise during beta-blockers + verapamil, exercise-induced arrhythmias were reduced: (1) Three patients had nonsustained VT on beta-blockers, and none of them had VT on combination therapy. (2) The number of ventricular ectopics during the whole exercise test went down from 78 +/- 59 beats to 6 +/- 8 beats; the ratio of ventricular ectopic to sinus beats during the 10-second period recorded at the time of the worst ventricular arrhythmia went down from 0.9 +/- 0.4 to 0.2 +/- 0.2. One patient with recurrent spontaneous VT leading to multiple shocks from her implanted cardioverter-defibrillator (ICD) despite maximal beta-blocker therapy (14 ICD shocks over 6 months while on beta-blockers) has remained free of arrhythmias (for 7 months) since the addition of verapamil therapy. CONCLUSIONS: This preliminary evidence suggests that beta-blockers and calcium blockers could be better than beta-blockers alone for preventing exercise-induced arrhythmias in CPVT.

Diastolic mitral regurgitation following transcatheter aortic valve replacement: Incidence, predictors, and association with clinical outcomes.

BACKGROUND: Diastolic mitral regurgitation (DMR) results from atrioventricular conduction disturbances, acute aortic regurgitation, and/or marked elevation of left ventricular filling pressure. Generally benign, in some clinical circumstances DMR has presumed to result in hemodynamic decompensation. The aforementioned causes of DMR are frequently encountered in patients treated by transcatheter aortic valve replacement (TAVR) but its clinical significance in this setting has not been studied. We sought to investigate the incidence of DMR and its prognostic implications following TAVR. METHODS: Baseline clinical and echocardiographic variables from a prospective TAVR registry were analyzed to determine the correlates of post-procedural DMR and its impact on late outcomes (all-cause mortality and the composite of mortality and readmission due to heart failure). RESULTS: Of 267 patients undergoing TAVR, post-procedural DMR was present in 25 (9.3%). Independent predictors of DMR included pacemaker implantation [OR=2.7 (95%CI 1.03-6.50)], post-procedural systolic MR and aortic regurgitation [OR=3.7 (1.20-10.80) and OR=4.1 (1.50-10.60), respectively], and use of self-expanding bioprostheses [OR=4.9 (1.60-21.0)]. The incidence of the combined endpoint of death and/or readmission for heart failure was higher in patients with versus those without DMR (25% vs. 41%, respectively, p=0.08), although this association did not attain statistical significance on multivariable analyses. Interaction term analysis indicated a trend toward a heightened risk for the composite endpoint among patients with post-procedural aortic regurgitation (≥moderate) in whom DMR occurred (χ2 2.94, p=0.09). CONCLUSIONS: Although DMR following TAVR is common (occurring in approximately 1 of 10 patients), it is not independently associated with an increased risk of death and/or readmission for heart failure. Therefore, DMR post TAVR is more likely a marker of cardiac dysfunction than a causative factor.

Discriminating Circulatory Problems From Deconditioning: Echocardiographic and Cardiopulmonary Exercise Test Analysis.

BACKGROUND: Discriminating circulatory problems with reduced stroke volume (SV) from deconditioning, in which the muscles cannot consume oxygen normally, by gas exchange parameters is difficult. METHODS: We performed combined stress echocardiography (SE) and cardiopulmonary exercise tests (CPET) in 110 patients (20 with normal effort capacity, 54 with attenuated SV response, and 36 with deconditioning) to evaluate multiple hemodynamic parameters and oxygen content difference (A-V.o2 Diff) in four predefined activity levels to assess which of the gas measures may help in the discrimination. RESULTS: Reduced anaerobic threshold (AT), low unchanging peak oxygen pulse, periodic breathing, shallow Δ peak oxygen consumption (V.o2)/Δwork rate (WR) ratio, and high expired volume per unit time/carbon dioxide production (V.e/V.co2) slope were all associated with abnormal SV response (P < .05 for all). The best discriminator was V.e/V.co2 slope to V.o2 ratio (≥ 2.7; area under the curve [AUC], 0.79; P < .0001). The optimal gas exchange model included ΔV.o2/ΔWR < 8.6; V.e/V.co2 slope to peak V.o2 ratio ≥ 2.7, and periodic breathing (AUC of 0.84; P < .0001). CONCLUSIONS: The best single gas exchange parameter to discriminate between circulatory problems and deconditioning is V.e/V.co2 slope to peak V.O2 ratio. Combining it with ΔV.o2/ΔWR and periodic breathing improves the discriminative ability.

Impact of Right Ventricular Dysfunction and Tricuspid Regurgitation on Outcomes in Patients Undergoing Transcatheter Aortic Valve Replacement.

BACKGROUND: Right ventricular (RV) dysfunction and tricuspid regurgitation (TR) may coexist with aortic stenosis. The aim of this study was to assess the association between RV dysfunction, TR, associated comorbidities, and outcomes following transcatheter aortic valve replacement (TAVR). METHODS: A retrospective analysis was conducted of baseline and 6-month clinical and echocardiographic parameters, including TR grade, RV size (grade, end-diastolic and end-systolic areas, annular diameter), and function (grade, tricuspid annular plane systolic excursion [TAPSE], fractional area change, Tei index), in 519 consecutive TAVR patients. RESULTS: The prevalence of moderate or greater TR was 11% (n = 59). Although TR was associated with increased mortality (P = .02) in unadjusted analysis, it did not demonstrate an independent association with outcome when adjusted for RV dysfunction (TAPSE; P = .30) or multiple clinical parameters (P ≥ .20). RV parameters associated with poor outcomes included TAPSE (P = .006) and Tei index (P = .005). TAPSE was associated with lower survival even when adjusted for TR (P = .009) and all clinical parameters (P = .01). Persistence of moderate or greater TR 6 months after TAVR seemed to be associated with lower survival (P = .02), even when adjusted for clinical and RV parameters (P = .07). CONCLUSIONS: TR in association with aortic stenosis is frequently progressive despite TAVR but is not independently associated with outcomes. RV function is a stronger driver of adverse outcomes compared with TR itself, and RV quantitative rather than qualitative evaluation is the key to stratify these patients.

Mechanisms of Effort Intolerance in Patients With Rheumatic Mitral Stenosis: Combined Echocardiography and Cardiopulmonary Stress Protocol.

OBJECTIVES: This study sought to evaluate mechanisms of effort intolerance in patients with rheumatic mitral stenosis (MS). BACKGROUND: Combined stress echocardiography and cardiopulmonary testing allows assessment of cardiac function, hemodynamics, and oxygen extraction (A-Vo2 difference). METHODS: Using semirecumbent bicycle exercise, 20 patients with rheumatic MS (valve area 1.36 ± 0.4 cm2) were compared to 20 control subjects at 4 pre-defined activity stages (rest, unloaded, anaerobic threshold, and peak). Various echocardiographic parameters (left ventricular volumes, ejection fraction, stroke volume, mitral valve gradient, mitral valve area, tissue s' and e') and ventilatory parameters (peak oxygen consumption [Vo2] and A-Vo2 difference) were measured during 8 to 12 min of graded exercise. RESULTS: Comparing patients with MS to control subjects, significant differences (both between groups and for group by time interaction) were seen in multiple parameters (heart rate, stroke volume, end-diastolic volume, ejection fraction, s', e', Vo2, and tidal volume). Exercise responses were all attenuated compared to control subjects. Comparing patients with MS and poor exercise tolerance (<80% of expected) to other subjects with MS, we found attenuated increases in tidal volume (p = 0.0003), heart rate (p = 0.0009), and mitral area (p = 0.04) in the poor exercise tolerance group. These patients also displayed different end-diastolic volume behavior over time (group by time interaction p = 0.05). In multivariable analysis, peak heart rate response (p = 0.01), tidal volume response (p = 0.0001), and peak A-Vo2 difference (p = 0.03) were the only independent predictors of exercise capacity in patients with MS; systolic pulmonary pressure, mitral valve gradient, and mitral valve area were not. CONCLUSIONS: In patients with rheumatic MS, exercise intolerance is predominantly the result of restrictive lung function, chronotropic incompetence, limited stroke volume reserve, and peripheral factors, and not simply impaired valvular function. Combined stress echocardiography and cardiopulmonary testing can be helpful in determining mechanisms of exercise intolerance in patients with MS.

Mechanisms of Effort Intolerance in Patients With Heart Failure and Borderline Ejection Fraction.

Combining echocardiography and cardiopulmonary stress testing allows noninvasive assessment of hemodynamics, and oxygen extraction (A-VO2 difference). We evaluated mechanisms of effort intolerance in patients with heart failure with borderline (40% to 49%) left ventricular ejection fraction (EF) (HF and Borderline Ejection fraction). We included 89 consecutive patients with HF and Borderline Ejection fraction (n = 25; 63.6 ± 14 years, 64% men), control subjects (n = 22), patients with HF with preserved EF (n = 26; EF ≥50%), and patients with HF with reduced EF (n = 16; <40%). Various echo parameters (left ventricular volumes, EF, stroke volume, mitral regurgitation [MR] volume, e', right ventricle end-diastolic area, and right ventricle end-systolic area), and ventilatory or combined parameters (peak oxygen consumption [VO2] and A-VO2 difference) were measured at 4 predefined activity stages. Effort-induced functional MR was frequent and more prevalent in HF and Borderline Ejection fraction than in all the other types of HF. In multivariable analysis heart rate response (p <0.0001), A-VO2 difference (p = 0.02), stroke volume (p = 0.002), and right ventricle end-systolic area were the only independent predictors of exercise capacity in HF and Borderline Ejection fraction but peak EF was not. In HF and Borderline Ejection fraction exercise intolerance is predominantly due to chronotropic incompetence, peripheral factors, and limited stroke volume reserve, which are related to right ventricle dysfunction and functional MR but not to left ventricular ejection fraction. Combined testing can be helpful in determining mechanisms of exercise intolerance in HF and Borderline Ejection fraction.