Persistent anemia after implantation of the total artificial heart

BackgroundThe total artificial heart (TAH) replaces the heart with 2 pneumatic pumps and 4 tilting disk mechanical valves. It was hypothesized that patients receiving TAH support have persistent hemolysis that resolves after heart transplantation (HT).Methods and ResultsHematocrit (HCT) was compared in patients on TAH to left ventricular assist device (LVAD) support for bridge to HT. Data were compared with t tests. The TAH (n = 36; mean age 47 ± 13 years) and LVAD patients (n = 14; mean age 53 ± 12 years) were supported for a median of 83 (interquartile range [IQR] 43–115) and 106 days (IQR 84–134), respectively. Hematocrit was similar between the TAH and LVAD patients (34 ± 6% vs 37 ± 5%; P = .07) at baseline. After placement, TAH patients had lower HCT at 2 (20 ± 2% vs 24 ± 3%), 4 (22 ± 3% vs 26 ± 3%), 6 (22 ± 4% vs 30 ± 4%), and 8 weeks (23 ± 4% vs 33 ± 5%; P < .001 for all). There were no differences in HCT at 1 (30 ± 4% vs 29 ± 7%; P = .42) and 3 months (35 ± 7% vs 35 ± 4%; P = .98) after removal of the devices for HT. TAH patients had undetectable haptoglobin in 96% of assessments, increased lactate dehydrogenase (1,128 ± 384 units/L), and detectable plasma free hemoglobin in 40% of measurements (21 ± 15 mg/dL). High sensitivity C-reactive protein (52 ± 50 mg/dL) was elevated, and reticulocyte production index was decreased (1.6 ± 0.6).ConclusionsPatients implanted with a TAH have persistent anemia that resolves only after HT. The association of hemolysis, ineffective erythropoiesis, and inflammation with the TAH warrants further study.     

Postoperative Right Ventricular Failure After Left Ventricular Assist Device Placement is Predicted by Preoperative Echocardiographic Structural,Hemodynamic, and Functional Parameters

BackgroundRight ventricular failure (RVF) after left ventricular assist device (LVAD) implantation results in significant morbidity and mortality. Preoperative parameters from transthoracic echocardiography (TTE) that predict RVF after LVAD implantation might identify patients in need of temporary or permanent right ventricular (RV) mechanical or inotropic support.Methods and ResultsRecords of all patients who had preoperative TTE before implantation of a permanent LVAD at our institution from 2008 to 2011 were screened, and 55 patients (age 54 ± 16 years, 71% male) were included: 26 had LVAD implantation alone with no postoperative RVF, 16 had LVAD implantation alone but experienced postoperative RVF, and 13 had initial biventricular assist devices (BIVADs). The LVAD with RVF and BIVAD groups (RVF group) were pooled for comparison with the LVAD patients without RVF (No RVF group). RV fractional area change (RV FAC) was significantly lower in the RVF group versus the No RVF group (24% vs 30%; P = .04). Tricuspid annular plane systolic excursion was not different among the groups (1.6 cm vs 1.5 cm; P = .53). Estimated right atrial pressure (RAP) was significantly higher in the RVF group versus the No RVF group (11 mm Hg vs 8 mm Hg; P = .04). Left atrial volume (LAV) index was lower in patients with RVF versus No RVF (27 mL/m² vs 40 mL/m²; P = .008). Combining RV FAC, estimated RAP, and LAV index into an echocardiographic scoring system revealed that the TTE score was highly predictive of RVF (5.0 vs 2.8; P = .0001). In multivariate models combining the TTE score with clinical variables, the score was the most predictive of RVF (odds ratio 1.66, 95% confidence interval 1.06–2.62).ConclusionsPreoperative RV FAC, estimated RAP, and LAV index predict postoperative RVF in patients undergoing LVAD implantation. These parameters may be combined into a simple echocardiographic scoring system to provide an additional tool to risk-stratify patients being evaluated for LVAD implantation.     

Effect of Left Ventricular Assist Device Placement on Preexisting Implantable Cardioverter-defibrillator Leads

BackgroundThe left ventricular assist device (LVAD) is a therapy for patients with end-stage heart failure, many of whom have a preexisting implantable cardioverter-defibrillator (ICD). We investigated whether the implantation of a LVAD affects ICD function.Methods and ResultsPatients implanted with a LVAD between September 2000 and February 2009 were studied. Right ventricular (RV), right atrial, and left ventricular lead impedance, sensing, and capture thresholds were recorded before and after LVAD placement and subsequent lead-related interventions were noted. Of the 61 patients receiving a LVAD, data were collected from 30 patients who had preexisting ICDs. Significant pre-post differences were noted for all RV lead parameters: sensing amplitude decreased from 9.2 ± 3.1 to 5.7 ± 3.6 millivolts (P < .001); impedance decreased from 479 ± 118 to 418 ± 94 ohms (P = .008); and threshold increased from 4.3 ± 6.7 to 11.0 ± 16.8 microjoules (P = .021). As a result of alterations in lead parameters, 4 patients (13%) required lead revisions and 6 patients (20%) required ICD testing.ConclusionsDifferences in ICD lead function were observed after LVAD placement resulting in clinically significant interventions. These data suggest that ICD interrogation be performed post-LVAD placement and that patients be counseled for the potential need for lead revisions and ICD testing when consented for a LVAD.     

Impact of QRS Duration and Ventricular Pacing on Clinical and Arrhythmic Outcomes in Continuous Flow Left Ventricular Assist Device Recipients: A Multicenter Study

ObjectivesWide QRS duration and ventricular pacing are common in recipients of continuous-flow left ventricular assist devices (CF-LVADs) but their impact on outcomes remains unclear. We assessed the clinical and arrhythmic outcomes of CF-LVAD patients with wide QRS or right ventricular (RV) pacing at baseline, compared with those with narrow QRS and those with continued cardiac resynchronization therapy (CRT).Methods and ResultsA total of 520 patients (57 ± 13 years) with an implantable cardioverter-defibrillator (ICD) (n = 240) or CRT-defibrillator (n = 280) who underwent CF-LVAD implantation at 5 centers in 2007–2015 were studied. Patients were divided into 3 groups: ICD-N (QRS ≤120 ms; n = 134), ICD-W (QRS >120 ms; n = 106), and CRT (n = 280). Mortality, hospitalization, and ventricular arrhythmia (VA) incidence were compared among the groups. Baseline QRS duration was different among the groups (100 ± 13 [ICD-N] vs 155 ± 26 [ICD-W] vs 159 ± 29 ms [CRT]; P < .0001). In the ICD-W group, 37 (35%) had >80% RV pacing at baseline. Median biventricular pacing in the CRT group was 96%. Over 523 days of CF-LVAD support, Kaplan-Meier analysis showed no difference in survival among groups (log rank P = .9). According to multivariate Cox regression, wide QRS duration and RV pacing were not associated with survival. QRS narrowed during CF-LVAD support in the ICD-W and CRT groups but was not associated with improved survival (P = .9). No differences were noted among the groups in hospitalizations (P = .9), VA (P = .2), or ICD shocks (P = .06).ConclusionsIn this large CF-LVAD cohort, a wide QRS duration, high percentage of RV pacing at baseline, and changes in QRS duration after LVAD implantation were not associated with survival. Continued CRT after CF-LVAD implantation also was not associated with improved survival or HF hospitalizations.     

Reduced Handgrip Strength as a Marker of Frailty Predicts Clinical Outcomes in Patients With Heart Failure Undergoing Ventricular Assist Device Placement

BackgroundHeart failure (HF) is associated with the derangement of muscle structure and metabolism, contributing to exercise intolerance, frailty, and mortality. Reduced handgrip strength is associated with increased patient frailty and higher morbidity and mortality. We evaluated handgrip strength as a marker of muscle function and frailty for prediction of clinical outcomes after ventricular assist device (VAD) implantation in patients with advanced HF.Methods and ResultsHandgrip strength was measured in 72 patients with advanced HF before VAD implantation (2.3 ± 4.9 days pre-VAD). We analyzed dynamics in handgrip strength, laboratory values, postoperative complications, and mortality. Handgrip strength correlated with serum albumin levels (r = 0.334, P = .004). Compared with baseline, handgrip strength increased post-VAD implantation by 18.2 ± 5.6% at 3 months (n = 29) and 45.5 ± 23.9% at 6 months (n = 27). Patients with a handgrip strength <25% of body weight had an increased risk of mortality, increased postoperative complications, and lower survival after VAD implantation.ConclusionPatients with advanced HF show impaired handgrip strength indicating a global myopathy. Handgrip strength <25% of body weight is associated with higher postoperative complication rates and increased mortality after VAD implantation. Thus, the addition of measures of skeletal muscle function underlying the frailty phenotype to traditional risk markers might have incremental prognostic value in patients undergoing evaluation for VAD placement.     

Right Ventricular Systolic and Diastolic Function as Assessed by Speckle-Tracking Echocardiography Improve With Prolonged Isolated Left Ventricular Assist Device Support

BackgroundRight ventricular (RV) failure is a major cause of morbidity and mortality after left ventricular assist device (LVAD) implantation. Whether RV function deteriorates with prolonged LVAD support is unknown. Speckle-tracking echocardiography provides a sensitive, noninvasive, reproducible, and quantitative assessment of RV systolic and diastolic function.MethodsEchocardiograms were retrospectively reviewed from before and after implantation of a Heartmate II LVAD. Speckle-tracking analysis was performed to measure RV longitudinal systolic strain, strain rate, and diastolic strain rate for each patient at baseline and over discrete time periods after LVAD implantation.ResultsSeventeen patients were included in the analysis, with an average follow-up after LVAD implantation of 234 ± 125 days. RV systolic strain improved in 15 patients, decreasing from −7.4 ± 2.3% to −9.7 ± 3.3% after LVAD (P = .026). Systolic strain rate improved in 11 patients, decreasing from −0.67 ± 0.25%/s to −0.96 ± 0.36%/s (P = .011). RV diastolic strain rate improved in 12 patients, increasing from 0.70 ± 0.33%/s to 1.02 ± 0.40%/s (P = .016).ConclusionsChronic LVAD support improves RV systolic and diastolic function in LVAD patients who did not require an RV assist device. Speckle-tracking echocardiography may offer a noninvasive technique for identifying and monitoring improvements in RV function in LVAD patients.     

Implantable Cardiac Defibrillators and Sudden Death in Recent Onset Nonischemic Cardiomyopathy: Results From IMAC2

BackgroundGiven the potential for recovery in recent onset nonischemic cardiomyopathy (ROCM), the timing and need for implantable cardioverter-defibrillator (ICDs) remains controversial. We examined the utilization of ICDs and the impact on survival for subjects with ROCM.Methods and ResultsAn National Heart, Lung, and Blood Institute sponsored registry enrolled 373 subjects with ROCM, all with a left ventricular ejection fraction (LVEF) ≤0.40 and ≤6 months of symptoms. The mean age was 45 ± 14 years, 38% were female, 21% black, 75% New York Heart Association II/III, and the mean LVEF was 0.24 ± 0.08. Survival was comparable for subjects with an ICD within 1 month of entry (n = 43, 1/2/3 year % survival = 97/97/92) and those with no ICD at 1 month (n = 330, % survival = 98/97/95, P = .30) and between those with and without an ICD at 6 months (ICD, n = 73, 1/2/3 year % survival = 98/98/95; no ICD, n = 300, % survival = 98/96/95, P = .95). There were only 6 sudden cardiac deaths (SCD) noted (% survival free from SCD = 99/98/97) and these occurred in 1.9% of subjects without ICD and 0.9% of those with a device (P = .50).ConclusionsIn a multicenter cohort of ROCM the risk of SCD was low at 1% per year. Early ICD placement did not impact survival and can be deferred while assessing potential for myocardial recovery.     

Mid-term survival after continuous-flow left ventricular assist device versus heart transplantation

There is a paucity of data about mid-term outcome of patients with advanced heart failure (HF) treated with left ventricular assist device (LVAD) in Europe, where donor shortage and their aging limit the availability and the probability of success of heart transplantation (HTx). The aim of this study is to compare Italian single-centre mid-term outcome in prospective patients treated with LVAD vs. HTx. We evaluated 213 consecutive patients with advanced HF who underwent continuous-flow LVAD implant or HTx from 1/2006 to 2/2012, with complete follow-up at 1 year (3/2013). We compared outcome in patients who received a LVAD (n = 49) with those who underwent HTx (n = 164) and in matched groups of 39 LVAD and 39 HTx patients. Patients that were treated with LVAD had a worse risk profile in comparison with HTx patients. Kaplan–Meier survival curves estimated a one-year survival of 75.5 % in LVAD vs. 82.3 % in HTx patients, a difference that was non-statistically significant [hazard ratio (HR) 1.46; 95 % confidence interval (CI) 0.74–2.86; p = 0.27 for LVAD vs. HTx]. After group matching 1-year survival was similar between LVAD (76.9 %) and HTx (79.5 %; HR 1.15; 95 % CI 0.44–2.98; p = 0.78). Concordant data was observed at 2-year follow-up. Patients treated with LVAD as bridge-to-transplant indication (n = 22) showed a non significant better outcome compared with HTx with a 95.5 and 90.9 % survival, at 1- and 2-year follow-up, respectively. Despite worse preoperative conditions, survival is not significantly lower after LVAD than after HTx at 2-year follow-up. Given the scarce number of donors for HTx, LVAD therapy represents a valid option, potentially affecting the current allocation strategy of heart donors also in Europe.     

Short-term Prognostic Value of Heart Failure Diagnosis in a Contemporary Cohort of Patients With Adult Congenital Heart Disease

BackgroundHeart failure (HF) is the primary cause of premature death in adult congenital heart disease (ACHD). This study aimed to describe the impact of a HF diagnosis on short-term prognosis and to investigate the added prognostic value of an HF diagnosis to the ACHD Anatomic and Physiologic classification (ACHD-AP).MethodsThis study included 3995 patients followed in a tertiary care centre (last follow-up after January 1, 2010). Survival curves were plotted, and predictors of the primary end point (death, heart transplantation, or ventricular assist device [VAD]) were identified with the use of Cox proportional hazard models and compared with the use of Harrell’s C-statistic.ResultsMean age at baseline was 35.7 ± 13.3 years. The prevalence of ACHD-HF was 6.4%. During a median follow-up of 3.1 years (IQR 2.1-3.6 years), 27.3% of ACHD-HF patients reached the primary end point, compared with 1.4% of ACHD patients without HF. Event-free survivals were 78.3%, 61.9%, and 57.5% at 1, 3, and 5 years in ACHD-HF patients, compared with 99.3%, 98.3%, and 98.0% in ACHD patients without HF (P < 0.001). An HF diagnosis (HR 6.9, 95% CI 4.3-11.2) and the physiologic classification (HR 2.6, 95% CI 1.9-3.7) were independently associated with the primary end point. The addition of HF to the ACHD-AP classification yielded a Harrell’s C-index of 0.8631, providing a significant improvement over the ACHD-AP classification alone (P = 0.0003).ConclusionsThe risk of mortality, transplantation, or VAD is increased in ACHD-HF patients. An HF diagnosis appears to be a valuable prognostic marker in addition to the ACHD-AP classification.     

Pericardial Adipose Tissue Volume and Left Ventricular Assist Device-Associated Outcomes

BackgroundPericardial adipose tissue (PAT) is associated with adverse cardiovascular outcomes in those with and without established heart failure (HF). However, it is not known whether PAT is associated with adverse outcomes in patients with end-stage HF undergoing left ventricular assist device (LVAD) implantation. This study aimed to evaluate the associations between PAT and LVAD-associated outcomes.Methods and ResultsWe retrospectively measured computed tomography-derived PAT volumes in 77 consecutive adults who had available chest CT imaging prior to HeartMate 3 LVAD surgery between October 2015 and March 2019 at Duke University Hospital. Study groups were divided into above-median (≥219 cm³) and below-median (<219 cm³) PAT volume. Those with above-median PAT had a higher proportion of atrial fibrillation, chronic kidney disease and ischemic cardiomyopathy. Groups with above-median vs below-median PAT had similar Kaplan-Meier incidence rates over 2 years for (1) composite all-cause mortality, redo-LVAD surgery and cardiac transplantation (35.9 vs 32.2%; log-rank P = 0.65) and (2) composite incident hospitalizations for HF, gastrointestinal bleeding, LVAD-related infection, and stroke (61.5 vs 60.⁵%; log-rank P = 0.67).ConclusionsIn patients with end-stage HF undergoing LVAD therapy, PAT is not associated with worse 2-year LVAD-related outcomes. The significance of regional adiposity vs obesity in LVAD patients warrants further investigation.     

Sex Differences in the Long-term Prognosis of Dilated Cardiomyopathy

BackgroundDilated cardiomyopathy (DCM) represents a specific phenotype of heart failure. Sex differences in the long-term prognosis of patients with DCM are unknown. The aim of this study is to investigate the long-term prognostic role of gender in a large cohort of patients with DCM.MethodsA total of 1113 patients with DCM were prospectively enrolled. To investigate the impact of sex, a propensity score–matching analysis was performed on a sample of 586 patients. Univariable and multivariable Cox models and competing-risk analyses were estimated on both cohorts for the following outcome measures: (1) all-cause mortality/heart transplantation (HTx)/ventricular assist device (VAD); (2) cardiovascular mortality/HTx/VAD; and (3) sudden cardiac death or malignant ventricular arrhythmias.ResultsWomen were older than men (50 ± 15 years vs 47 ± 15 years, respectively, P = 0.004) and more frequently had moderate to severe left ventricular dilation (P < 0.001) and left bundle branch block (P = 0.019). At multivariable analyses, male sex was independently associated with all considered outcome measures in the total cohort. At propensity score–matching analysis, over a median follow-up of 126 months (interquartile range, 62-201), 96 men (33%) vs 66 women (22%) experienced all-cause mortality/HTx/VAD (P = 0.03), 95 men (32%) vs 57 women (20%) experienced cardiovascular mortality/HTx/VAD (P = 0.025), and 46 men (16%) vs 28 women (10%) experienced sudden cardiac death/malignant ventricular arrhythmias (P = 0.07).ConclusionThe long-term outcomes of women affected by DCM are more favourable than those of men, and sex emerged as an important independent factor, particularly for cardiovascular outcomes.     

Abnormalities of Calcium Handling Proteins in Skeletal Muscle Mirror Those of the Heart in Humans With Heart Failure: A Shared Mechanism?

BackgroundIn the failing human heart, abnormalities of Ca²⁺ cycling have been described, but there is scant knowledge about Ca²⁺ handling in the skeletal muscle of humans with heart failure (HF). We tested the hypothesis that in humans with HF, Ca²⁺ cycling proteins in skeletal muscle are abnormal.Methods and ResultsTen advanced HF patients (50.4 ± 3.7 years), and 9 age-matched controls underwent vastus lateralis biopsy. Western blot analysis showed that sarco(endo)plasmic reticulum Ca²⁺-ATPase (SERCA)2a, which is responsible for Ca²⁺ sequestration into the sarcoplasmic reticulum(SR), was lower in HF versus controls (4.8 ± 0.5 vs 7.5 ± 0.8 AU, P = .01). Although phospholamban (PLN), which inhibits SERCA2a, was not different in HF versus controls, phosphorylation (SER16 site) of PLN, which relieves this inhibition, was reduced (0.8 ± 0.1 vs 3.9 ± 0.9 AU, P = .004). Dihydropyridine receptors were reduced in HF, (2.1 ± 0.4 vs 3.6 ± 0.5 AU, P = .04). We tested the hypothesis that these abnormalities of Ca²⁺ handling protein content and regulation were due to increased oxidative stress, but oxygen radical scavenger proteins were not elevated in the skeletal muscle of HF patients.ConclusionIn chronic HF, marked abnormalities of Ca²⁺ handling proteins are present in skeletal muscle, which mirror those in failing heart tissue. This suggests a common mechanism, such as chronic augmentation of sympathetic activity and autophosphorylation of Ca²⁺-calmodulin-dependent-protein kinase II.     

The Effects of Race on Peak Oxygen Consumption and Survival in Patients With Systolic Dysfunction

BackgroundThe relationship of peak exercise oxygen consumption (VO₂) to survival in black heart failure (HF) patients is not well established. We examined the effects of race on peak VO₂ values and survival in HF patients with systolic dysfunction.Methods and ResultsThis study evaluated consecutive ambulatory HF patients who underwent symptom-limited stress tests with breath-by-breath expired gas analyses using ramped treadmill protocols. The relationship between cardiopulmonary exercise parameters and patient transplant-free survival was assessed by race. This study included 580 HF patients (mean age 52 ± 12 years; 28% females; 22% blacks; mean left ventricular ejection fraction 26 ± 12%; mean body mass index 28.7 ± 5.4; 73% on β-blocker). Black patients had a significantly lower peak VO₂ than white patients (14.2 ± 5.2 versus 16.4 ± 7.0; P < .0001), despite adjusting for identified covariates. However, there was no significant difference in the 1-year transplant-free survival between black and white HF patients (87% versus 85%; P = NS). Peak VO₂ was significantly associated with survival in both racial groups.ConclusionsBlack HF patients had significantly lower peak VO₂, but yet had equivalent survival rates at 1 year. Further study is warranted to clarify the impact of these racial differences on the timing of cardiac transplantation black HF patients.     

Long‐Term Survival of Routine Implantable Cardioverter/Defibrillator Recipients Appears to be Significantly Impaired with Concomitant Diuretics and Improved with Aldosterone Antagonists

Evidence‐based treatment for heart failure (HF) comprises beta‐blockers, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and aldosterone receptor antagonists (ARA). Diuretics (DR) are prescribed in acute and chronic HF, but their impact on survival and ventricular tachyarrhythmias (VT/VF) is unclear. The present observational study aims to examine the influence of DR and ARA on survival and appropriate cardioverter/defibrillator (ICD) treatment episodes in routine ICD patients. In 352 consecutive ICD patients (291 men, 60 ± 12 years, LVEF 34 ± 15%, follow‐up 37 ± 19 months) overall survival and the time to a first appropriate VT/VF episode were assessed. Electrograms were validated. Potassium and creatinine serum levels and the medical treatment regimen for heart failure were documented at baseline. Multivariate Cox regression analyses revealed significantly worse survival for patients with DR compared to those without DR (OR 0.24, CI 0.08–0.76, P= 0.016), whereas the group with ARA had better survival compared to patients without (OR 2.05, CI 1.02–4.10, P= 0.04). Patient groups did not differ regarding survival without incident VT/VF (DR+ vs. DR– OR 1.10, CI 0.67–1.83, P= 0.70; OR 0.66, CI 0.40–1.09, P= 0.10). Long‐term survival appears to be compromised in ICD patients receiving concomitant DR, but is favorably influenced by ARA, although VT/VF incidence does not differ. Randomized analyses are warranted to assess long‐term prognostic effects of DR in HF.     

Hemodynamic determinants of the abnormal cardiopulmonary exercise response in heart failure with preserved left ventricular ejection fraction

BackgroundThe cardiopulmonary exercise testing (CPET) response in heart failure with preserved left ventricular ejection fraction (HFPEF) is incompletely understood. We aimed to describe the CPET response in HFPEF and to assess its invasive hemodynamic determinants.Methods and ResultsTen patients with HFPEF and 8 asymptomatic controls underwent resting and exercise right heart catheterization and maximal symptom-limited CPET. The slope of the minute ventilation/carbon dioxide production relationship (VE/VCO₂ slope; 34.3 ± 5.4 vs. 28.4 ± 3.4; P = .02) was steeper, peak oxygen consumption (peak VO₂; 15.1 ± 4.9 vs. 26.6 ± 12.5 mL1kg^-11min^-1; P = .02) was lower, and heart rate recovery 1 minute after exercise termination (HRR-1; 10 ± 5 vs. 27 ± 10 beats/min; P < .001) was slower in HFPEF compared to controls. A steeper VE/VCO₂ slope (r = 0.67, P = .002), lower peak VO₂ (r = ?0.48, P = .04), and slower HRR-1 (r = ?0.58, P = .02) were significantly related to a higher ratio of the change in pulmonary capillary wedge pressure per change in work rate as a measure of the left ventricular pressure volume relationship.ConclusionsIn HFPEF patients, fundamental alterations in the CPET profile occur and these may, in part, result from the rapid rise in left ventricular filling pressures which accompanies exercise in these patients.     

Long-term prognostic value of CA 125 serum levels in mild to moderate heart failure patients

BackgroundPlasma levels of tumor marker carbohydrate 125 antigen (CA 125) have been found elevated among patients with advanced heart failure (HF). We evaluated the prognostic value of CA125 in a population of patients with mild to moderate HF.Methods and ResultsSerum levels of CA 125 were obtained in 102 patients with mild to moderate HF from idiopathic (48%) or ischemic (52%) dilated cardiomyopathy (age 64 ± 10.4 years, left ventricular ejection fraction: 34.4 ± 8.5%), under optimized medical therapy. During follow-up (43 ± 15 months), 16 (15.7%) cardiovascular deaths and 23 (22.5%) cardiovascular deaths + HF hospitalizations were recorded. Considering cardiac death, comparison of Kaplan-Meier survival curves by the log-rank test showed that patients with CA 125 levels higher than the cut-off value (30 U/mL) had a worse survival (P < .0001). This was observed also when considering cardiovascular death+ HF hospitalizations as the secondary end point (P = .0003). Event-free survival was assessed by Kaplan-Meier method and log-rank test. Multivariable Cox proportional stepwise hazards regression analysis was performed and showed that CA 125 and systolic pulmonary artery pressure (sPAP) were significantly associated with the risk of cardiovascular deaths + HF hospitalizations (HR 1.01, 95% CI 1.02–1.06, and HR 1.07, 95% CI 1.02–1.1, P < .001, respectively).ConclusionsIn mild-to-moderate HF patients under optimized therapy, higher plasma CA 125 levels are an effective long-term prognostic marker in forecasting cardiovascular events and HF hospitalization and may contribute to a better risk stratification.     

Beta-blockers and Ambulatory Inotropic Therapy

BackgroundContinuous infusion of ambulatory inotropic therapy (AIT) is increasingly used in patients with end-stage heart failure (HF). There is a paucity of data concerning the concomitant use of beta-blockers (BB) in these patients.MethodsWe retrospectively reviewed all patients discharged from our institution on AIT. The cohort was stratified into 2 groups based on BB use. The 2 groups were compared for differences in hospitalizations due to HF, ventricular arrhythmias and ICD therapies (shock or antitachycardia pacing).ResultsBetween 2010 and 2017, 349 patients were discharged on AIT (95% on milrinone); 74% were males with a mean age of 61 ± 14 years. BB were used in 195 (56%) patients, whereas 154 (44%) did not receive these medications. Patients in the BB group had longer duration of AIT support compared to those in the non-BB group (141 [1–2114] vs 68 [1–690] days). After adjusting for differences in baseline characteristics and indication for AIT, patients in the BB group had significantly lower rates of hospitalizations due to HF (hazard ratio [HR] 0.61 (0.43–0.86); P = 0.005), ventricular arrhythmias (HR 0.34 [0.15–0.74]; P = 0.007) and ICD therapies (HR 0.24 [0.07–0.79]; P = 0.02).ConclusionIn patients with end-stage HF on AIT, the use of BB with inotropes was associated with fewer hospitalizations due to HF and fewer ventricular arrhythmias.     

Effects of Trimetazidine in Nonischemic Heart Failure: A Randomized Study

ObjectivesHeart failure (HF) is associated with changes in myocardial metabolism that lead to impairment of contractile function. Trimetazidine (TMZ) modulates cardiac energetic efficiency and improves outcomes in ischemic heart disease. We evaluated the effects of TMZ on left ventricular ejection fraction (LVEF), cardiac metabolism, exercise capacity, O₂ uptake, and quality of life in patients with nonischemic HF.Methods and ResultsSixty patients with stable nonischemic HF under optimal medical therapy were included in this randomized double-blind study. Patients were randomized to TMZ (35 mg orally twice a day) or placebo for 6 months. LVEF, 6-minute walk test (6MWT), maximum O₂ uptake in cardiopulmonary exercise test, different markers of metabolism, oxidative stress, and endothelial function, and quality of life were assessed at baseline and after TMZ treatment. Left ventricular peak glucose uptake was evaluated with the use of the maximum standardized uptake value (SUV) by 18-fluorodeoxyglucose positron emission tomography (¹⁸FDG-PET). Etiology was idiopathic in 85% and hypertensive in 15%. Both groups were similar in age, functional class, LVEF, and levels of N-terminal pro–B-type natriuretic peptide at baseline. After 6 months of TMZ treatment, no changes were observed in LVEF (31 ± 10% vs 34 ± 8%; P = .8), 6MWT (443 ± 25 m vs 506 ± 79 m; P = .03), maximum O₂ uptake (19.1 ± 5.0 mL kg⁻¹ min⁻¹ vs 23.0 ± 7.2 mL kg⁻¹ min⁻¹; P = .11), functional class (percentages of patients in functional classes I/II/III/IV 10/3753/0 vs 7/40/50/3; P = .14), or quality of life (32 ± 26 points vs 24 ± 18 points; P = .25) in TMZ versus placebo, respectively. In the subgroup of patients evaluated with ¹⁸FDG-PET, no significant differences were observed in SUV between both groups (7.0 ± 3.6 vs 8.2 ± 3.4 respectively; P = .47).ConclusionsIn patients with nonischemic HF, the addition of TMZ to optimal medical treatment does not result in significant changes of LVEF, exercise capacity, O₂ uptake, or quality of life.     

The Presence of Electromechanical Mismatch In Nonischemic Dilated Cardiomyopathy Is Associated With Ventricular Repolarization Instability

BackgroundWe analyzed electromechanical mismatch (EMM) and its relationship to ventricular repolarization in patients with nonischemic dilated cardiomyopathy (DCM).Methods and ResultsIn 39 DCM patients with left ventricular ejection fraction (LVEF) <40% and New York Heart Association functional class ≥III, electroanatomic mapping was used to quantify areas of EMM. High-resolution electrocardiograph was used to measure heart rate variability (HRV) and QT variability index (QTVI). EMM was present in 22 patients (56%, group 1), whereas 17 patients presented no mismatched segments (44%, group 2). The groups did not differ in age (56 ± 10 years in group 1 vs 57 ± 7 years in group 2; P = .82), sex (male: 82% vs 94%; P = .40), LVEF (27 ± 8% vs 25 ± 6%; P = .18), or N-terminal pro–B-type natriuretic peptide (2,350 pg/mL vs 2,831 pg/mL; P = .32). Although heart rate and HRV were similar in both groups (rate: 80 ± 20 beats/min in group 1 vs 74 ± 19 beats/min in group 2 [P = .47]; standard deviation of normal-to normal RR intervals: 106 ± 79 vs 88 ± 115 [P = .61]), we found significantly higher QTVI values in patients from group 1 (−1.15 ± 0.46 vs −1.62 ± 0.51 in group 2; P = .005). In patients with implantable cardioverter-defibrillators, ventricular arrhythmias recorded ≤1 year before enrollment were more frequent in group 1 than in group 2 (58% vs 13%; P = .02).ConclusionsEMM is present in a majority of patients with DCM and is associated with ventricular repolarization instability.     

Differences in Clinical Profile of African-American Women With Peripartum Cardiomyopathy in the United States

BackgroundPeripartum cardiomyopathy (PPCM) is a rare and heterogeneous disease with a higher prevalence in African Americans (AAs) in the USA. The clinical features and prognosis of PPCM in AAs have not been sufficiently characterized.MethodsWe studied 52 AA patients with PPCM and compared clinical characteristics and outcome with those of 104 white patients.ResultsAA patients were significantly younger (26 ± 7 vs 30 ± 6 years; P < .001), had a higher prevalence of gestational hypertension (61% vs 41%; P = .03), and were diagnosed more commonly postpartum rather then antepartum (83% vs 64%; P = .03). The rate of left ventricular (LV) recovery (LV ejection fraction [LVEF] ≥50%) was significantly lower in AAs (40% vs 61%; P = .02). AA women also had a larger LV end-diastolic diameter (57 ± 10 vs 51 ± 6 mm; P = .004) as well as lower LVEF (40% ± 16.7% vs 46% ± 14%; P = .002) at the last follow-up. Moreover, AA patients had a significantly higher incidence of the combined end points of mortality and cardiac transplantation (P = .03) and showed a strong trend (P = .09) for increased mortality.ConclusionsAA patients with PPCM in the USA have a different clinical profile and worse prognosis compared with white patients. Further research to evaluate potentially correctable causes for these differences is warranted.