Successful conservative management of left ventricular assist device candidates.

AIMS: Clinical trials comparing LVADs vs. conservative therapy were performed before the availability of novel medications or used suboptimal medical therapy. This study aimed to report that long-term stabilization of patients entering a left ventricular assist device (LVAD) programme is possible with the use of aggressive conservative therapy. This is important because the excellent clinical stabilization provided by LVADs comes at the expense of significant complications. METHODS AND RESULTS: This study was a single-centre prospective evaluation of consecutive patients with advanced heart failure (HF) fulfilling criteria for LVAD implantation based on clinical and echocardiographic characteristics, cardiopulmonary exercise test, and right heart catheterization results. Their initial therapy included inotropes, thiamine, beta-blockers, digoxin, spironolactone, hydralazine, and nitrates followed by the introduction of novel HF therapies. Coronary revascularization and cardiac resynchronization therapy were performed when indicated, and all patients were closely followed at our outpatient clinic. During the study period, 28 patients were considered suitable for LVAD implantation (mean age 63 ± 10.8 years, 92% men, 78% ischaemic, median HF duration 4 years). Clinical stabilization was achieved and maintained in 21 patients (median follow-up 20 months, range 9-38 months). Compared with baseline evaluation, cardiac index increased from 2.05 (1.73-2.28) to 2.88 (2.63-3.55) L/min/m2 , left ventricular end-diastolic diameter decreased from 65.5 (62.4-66) to 58.3 (53.8-62.5) mm, and maximal oxygen consumption increased from 10.1 (9.2-11.3) to 16.1 (15.3-19) mL/kg/min. Three patients died and only four ultimately required LVAD implantation. CONCLUSIONS: Notwithstanding the small size of our cohort, our results suggest that LVAD implantation could be safely deferred in the majority of LVAD candidates.

A multicenter evaluation of external outflow graft obstruction with a fully magnetically levitated left ventricular assist device.

BACKGROUND: The HeartMate 3 (HM 3; Abbott) left ventricular assist device (LVAD) has improved hemocompatibility-related adverse outcomes. In sporadic cases, external compression of the outflow graft causing obstruction (eOGO) can result from substance accumulation between the outflow graft and its bend relief. We sought to evaluate the prevalence, course, and clinical implications of eOGO in an international study. METHODS: A multicenter retrospective analysis of HM 3 LVADs implanted between November 2014 and April 2021 (n = 2108) was conducted across 17 cardiac centers in 8 countries. We defined eOGO as obstruction >25% in the cross-sectional area in imaging (percutaneous angiography, computed tomography, or intravascular ultrasound). The prevalence and annual incidence were calculated. Serious adverse events and outcomes (death, transplantation, or device exchange) were analyzed for eOGO cases. RESULTS: Of 2108 patients, 62 were diagnosed with eOGO at a median LVAD support duration of 953 (interquartile range, 600-1267) days. The prevalence of eOGO was 3.0% and the incidence at 1, 2, 3, 4, and 5 years of support was 0.6%, 2.8%, 4.0%, 5.2%, and 9.1%, respectively. Of 62 patients, 9 were observed, 27 underwent surgical revision, 15 underwent percutaneous stent implantation, 8 received a heart transplant, and 2 died before intervention. One patient underwent surgical revision and later stent implantation. The mortality with therapeutic intervention was 9/53 (17.0%). CONCLUSIONS: Although uncommon, HM 3 LVAD-supported patients might develop eOGO with an increasing incidence after 1 year of support. Although engineering efforts to reduce this complication are under way, clinicians must maintain a focus on early detection and remain vigilant.

Medical Therapy for Functional Mitral Regurgitation.

Functional mitral regurgitation (FMR) can be broadly categorized into 2 main groups: ventricular and atrial, which often coexist. The former is secondary to left ventricular remodeling usually in the setting of heart failure with reduced ejection fraction or less frequently due to ischemic papillary muscle remodeling. Atrial FMR develops due to atrial and annular dilatation related to atrial fibrillation/flutter or from increased atrial pressures in the setting of heart failure with preserved ejection fraction. Guideline-directed medical therapy is the first step and prevails as the mainstay in the treatment of FMR. In this review, we address the medical therapeutic options for FMR management and highlight a targeted approach for each FMR category. We further address important clinical and echocardiographic characteristics to aid in determining when medical therapy is expected to have a low yield and an appropriate window for effective interventional approaches exists.

Venoarterial Extracorporeal Membrane Oxygenation to Facilitate Transcutaneous Mitral Valve Replacement in Critical Mitral Stenosis.

Biological mitral valve restenosis after replacement in rheumatic heart disease is a rare complication. This case illustrates venoarterial extracorporeal membrane oxygenation to facilitate transcatheter mitral valve replacement in a patient with suprasystemic pulmonary pressure and cardiogenic shock with multiorgan failure secondary to critical mitral stenosis of a bioprosthetic valve.(Level of Difficulty: Advanced.).

Repetitive milrinone therapy in ambulatory advanced heart failure patients.

BACKGROUND: Advanced heart failure (HF) patients usually poorly tolerate guideline-directed HF medical therapy (GDMT) and suffer high rates of morbidity and mortality. The use of continuous inotropes in the outpatient settings is hampered by previous data showing excess morbidity. We aimed to assess the safety and efficacy of repetitive, intermittent, short-term intravenous milrinone therapy in advanced HF patients with an intention to introduce and up-titrate GDMT and improve functional class. HYPOTHESIS: Repetitive, intermittent milrinone therapy may assist with the stabilization of advanced HF patients. METHODS: Advanced HF patients treated with beta-blockers and implanted with defibrillators were initiated with repetitive, intermittent short-term intravenous milrinone therapy at our HF outpatient unit. Patients were prospectively followed with defibrillator interrogation, functional class assessment, B-natriuretic peptide (BNP) levels, and echocardiography parameters. RESULTS: The cohort included 24 patients with a mean 330 ± 240 days of milrinone therapy exposure. Mean age was 73 ± 6 years with male predominance (96%). Following milrinone therapy, median BNP levels decreased significantly (882 [286-3768] to 631 [278-1378] pg/ml, p = .017) with a significant reduction in the number of patients with New York Heart Association (NYHA) Class III and IV (p = .012, 0.013) and an increase in number of patients on GDMT. Importantly, the number of total sustained ventricular tachycardia events and HF hospitalizations did not change. CONCLUSIONS: In this small cohort of advanced HF, repetitive, intermittent, short-term milrinone therapy was found to be safe and potentially efficacious.

Intermittent inotropic therapy with levosimendan vs. milrinone in advanced heart failure patients.

AIMS: Routine, intermittent inotropic therapy (IIT) is still applied in advanced heart failure (HF) patients either as a bridge to definitive treatment or as a mean to improve quality of life (QOL), despite limited evidence to support its' use. Given recent reports of improved QOL and reduced HF hospitalization, with levosimendan compared with placebo in advanced HF patients, we aimed to assess the effects of switching a small group of milrinone-treated patients to levosimendan. This was performed as part of a protocol for changing our ambulatory HF clinic milrinone-based IIT to levosimendan. METHODS AND RESULTS: Single-centre study of consecutive ambulatory advanced HF patients that received ≥4 cycles of once-weekly milrinone IIT at our HF outpatient clinic, who were switched to levosimendan IIT. All patients had left ventricular ejection fraction ≤35%, elevated B-natriuretic peptide (BNP), and were in New York Heart Association Classes III-IV despite maximally tolerated guideline directed medical therapy. Patients were evaluated using BNP levels, echocardiography, cardio-pulmonary exercise test, and HF QOL questionnaire before and after 4 weeks of levosimendan IIT. The cohort included 11 patients, 10 (91%) were male and the mean age was 76 ± 12 years. After 4 weeks of levosimendan therapy, maximal O2 consumption improved in 8/9 (89%) by a mean of 2.28 mL/kg [95% CI -0.22-3.38, P = 0.05]. BNP levels decreased in 9/11 (82%) levosimendan treated patients, from a median of 1015 ng/L [261-1035] to 719 ng/L [294-739], (P < 0.01). QOL as measure by the EQ-5D-5L questionnaire improved in 8/11 (82%) patients after levosimendan IIT, by a median of two points [95% CO -4.14-0.37, P = 0.09]. On echocardiography, peak systolic annular velocity (S') increased after levosimendan IIT by an average of 3 cm/s [95% CI 0.16-2.10, P = 0.03]. CONCLUSIONS: In this small-scale study of ambulatory advanced HF patients, we observed improvements in right ventricular systolic function, maximal O2 consumption, and BNP after switching from milrinone to levosimendan based IIT.

Echocardiographic Killip Classification.

BACKGROUND: Although routine echocardiographic parameters such as ejection fraction are used to risk-stratify for death in patients referred for echocardiography, they have limited predictive value. The authors speculated that noninvasive hemodynamic echocardiographic data, assessing left ventricular filling pressure and output, stratified on the basis of the clinical Killip score, might have additive prognostic value on top of routine echocardiographic parameters. The authors created an echocardiographic correlate of this classification, using diastolic grade and stroke volume index (SVI) as indicators of pulmonary congestion and systemic perfusion, respectively, and evaluated the prognostic value of this correlate. METHODS: A retrospective study of consecutive patients (hospitalized or not) referred for echocardiography for a range of cardiac diagnoses in a tertiary medical center. A total of 556 patients in sinus rhythm who were evaluated by two sonographers, and reviewed by a single cardiologist, were included. Normal filling pressure and normal SVI (>35 mL/m2) defined echocardiographic Killip (eKillip) class 1. Patients with pseudonormal or restrictive diastolic patterns and normal SVI were ascribed to eKillip class 2 or 3, respectively. A pseudonormal or restrictive diastolic pattern and a subnormal SVI defined eKillip class 4. RESULTS: eKillip class 1 was present in 382 patients (68%); 115 (20%), 26 (5%), and 42 (7%) patients were in eKillip classes 2 to 4, respectively. Median follow-up time was 1,056 days (interquartile range, 729-1,390 days). A total of 105 deaths occurred. Univariate Cox regression analysis showed that eKillip class was associated with all-cause mortality; hazard ratios (HR) -2.73 (95% CI, 1.67-4.48), 3.19 (95% CI, 1.42-7.17), and 4.79 (95% CI, 2.58-8.89) for each eKillip class above 1 (P < .001). In a multivariate analysis adjusted for the Charlson comorbidity index, eKillip class remained independently associated with all-cause mortality (P = .04). CONCLUSIONS: eKillip class was associated with all-cause mortality among all patients undergoing echocardiography at a tertiary hospital.

Correlation between CT-derived cardiac chamber volume, myocardial injury and mortality in acute pulmonary embolism.

INTRODUCTION: The release of troponin in patients with acute pulmonary embolism (PE) is assumed to be secondary to elevated intracardiac chamber pressure. Since right ventricular (RV) hypertrophy does not develop in the acute setting, pressure overload correlates with chamber dilatation, causing myocardial injury. The aim of the present study was to investigate correlations between cardiac chamber volume, troponin and subsequent early mortality in patients with acute PE and refine risk stratification. MATERIALS AND METHODS: Patients who underwent a computerized tomographic pulmonary angiogram (CTPA) and a troponin test within 24 h of the CTPA were included. Automated software calculated the volumes of the four cardiac chambers indexed to body surface area (BSA) and correlated them to troponin and early all-cause mortality. RESULTS: The final cohort consisted of 370 patients (56% females) with acute PE. RV volume and right to left ventricular volume ratio (VVR) were the most significant indicators for elevated troponin (receiving operating characteristic [ROC] 0.796, confidence interval [CI]: 0.749-0.843, p < 0.001, and ROC 0.802, CI: 0.753-0.851, p < 0.001, respectively). VVR cutoff values, which are predictive of elevated troponins, correlated with higher 30-day mortality (odds ratio = 3.1, CI 1.5-6.7, p = 0.003) for a VVR >3 compared to a VVR <2. CONCLUSION: Cardiac chamber volume correlates to elevated troponin in patients with acute PE. A higher VVR reflects an increased likelihood for myocardial ischemia, as well as an increased short-term mortality risk. These data are available seconds after CTPA performance and may contribute to refining patients' risk stratification.

Outflow graft obstruction in patients with the HM 3 LVAD: A percutaneous approach.

BACKGROUND: The use of the HeartMate 3 (HM3) left ventricular assist device (LVAD) is expanding. Despite being associated with lower rates of adverse events and increased survival, outflow graft obstruction (OGO) has been reported in patients with HM3. The incidence and best management of this serious complication remain unclear. METHODS: We describe six cases of HM3 OGO occurring in five patients in our institutional HM3 cohort. Four cases underwent computed tomography angiography and in two percutaneous angiography was directly performed to confirm the diagnosis. In four cases, percutaneous repair of the OG was performed using common interventional cardiology (IC) techniques. RESULTS: Our institutional incidence of OGO was 7% (event rate of 0.05 per patient year); much higher than the previously reported incidence of 1.6%. All cases occurred in the bend relief covered segment. Only two patients had apparent OG twisting, and in two, OGO occurred despite placement of an anti-twist clip at the time of implant. External compression seems to play a role in most cases. Balloon "graftoplasty" and stent deployment via the femoral artery alleviated the obstruction and normalized LVAD flow in all patients who underwent percutaneous repair. The use of self-expanding stents allowed for downsizing of the procedural access site to 10 Fr. No serious procedure-related complications occurred. CONCLUSION: OGO is common in HM3 patients, external compression due to biomaterial accumulated surrounding the OG is a common etiology. Percutaneous repair using standard IC techniques is safe and feasible in cases of compression with or without partial twisting.

Diastolic function as an early marker for systolic dysfunction and all-cause mortality among cancer patients.

BACKGROUND: Increased survival among active cancer patients exposes a wide range of side effects, including cardiotoxicity, manifested by systolic dysfunction and associated with morbidity and mortality. Early diagnosis of subclinical function changes and cardiac damage is essential in the management of these patients. Diastolic dysfunction is considered common among cancer patients; however, its effect on systolic dysfunction or mortality is still unknown. METHODS: Data were collected as part of the Israel Cardio-Oncology Registry, enrolling and prospectively following all patients evaluated in the cardio-oncology clinic in the Tel Aviv Sourasky Medical Center. All patients underwent echocardiographic examinations including evaluation of diastolic parameters and global longitudinal strain (GLS). Systolic dysfunction was defined as either an absolute reduction >10% in left ventricular ejection fraction to a value below 53% or GLS relative reduction >10% between the 1st and 3rd echocardiography examinations. RESULTS: Overall, 190 active cancer patients were included, with a mean age of 58 ± 15 years and a female predominance (78%). During a median follow-up of 243 days (interquartile ranges [IQR]: 164-401 days), 62 (33%) patients developed systolic dysfunction. Over a median follow-up of 789 days (IQR: 521-968 days), 29 (15%) patients died. There were no significant differences in baseline cardiac risk factors between the groups. Using multivariate analysis, E/e' lateral and e' lateral emerged as significantly associated with systolic dysfunction development and all-cause mortality (P = .015). CONCLUSION: Among active cancer patients, evaluation of diastolic function may provide an early marker for the development of systolic dysfunction, as well as all-cause mortality.

C-Reactive Protein Velocity and the Risk of New Onset Atrial Fibrillation among ST Elevation Myocardial Infarction Patients.

BACKGROUND: Elevated C-reactive protein (CRP) was shown to be associated with an increased risk for new-onset atrial fibrillation (AF) in ST elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI); however, the optimal time frame to measure CRP for risk stratification is not known. OBJECTIVES: To evaluate the relation between the change in CRP over time (CRP velocity [CRPv]) and new-onset AF among STEMI patients treated with primary PCI. METHODS: We included 801 STEMI patients who underwent PCI between 2007 and 2017 and had their CRP measured with a wide range assay (wr-CRP) at least twice during the 24 hours after admission. CRPv was defined as the change in wr-CRP concentration (mg/l) divided by the change in time (in hours) between the two measurements. Patient medical records were reviewed for occurrence of new-onset AF. RESULTS: New onset AF occurred in 45 patients (6%). Patients with new onset AF had significantly higher median CRPv (1.27 vs. 0.43 mg/l/h, P = 0.002). New-onset AF during hospitalization occurred in 3.4%, 4.5 %, and 9.1% of patients in the first, second and third CRPv tertiles, respectively (P for trend = 0.006). In a multivariable logistic regression, adjusting for clinical variables the odds ratios for new onset AF was 1.93 (95% confidence interval 1.0-3.59, P = 0.04) for patients in the third CRPv tertile. CONCLUSIONS: CRPv might be an independent and rapidly measurable biomarker for new-onset AF following primary PCI in STEMI patients.

Cancer Therapeutics-Related Cardiac Dysfunction among Patients with Active Breast Cancer: A Cardio-Oncology Registry.

BACKGROUND: Progress in the treatment of breast cancer has led to substantial improvement in survival, but at the cost of increased side effects, with cardiotoxicity being the most significant one. The commonly used definition is cancer therapeutics-related cardiac dysfunction (CTRCD), defined as a left ventricular ejection fraction reduction of > 10%, to a value below 53%. Recent studies have implied that the incidence of CTRCD among patients with breast cancer is decreasing due to lower doses of anthracyclines and low association to trastuzumab and pertuzumab treatment. OBJECTIVES: To evaluate the prevalence of CTRCD among patients with active breast cancer and to identify significant associates for its development. METHODS: Data were collected as part of the Israel Cardio-Oncology Registry, which enrolls all patients who are evaluated at the cardio-oncology clinic at our institution. Patients were divided to two groups: CTRCD and no-CTRCD. RESULTS: Among 103 consecutive patients, five (5%) developed CTRCD. There were no significant differences in the baseline cardiac risk factors between the groups. Significant correlations of CTRCD included treatment with trastuzumab (P = 0.001) or pertuzumab (P < 0.001), lower baseline global longitudinal strain (GLS) (P = 0.016), increased left ventricular end systolic diameter (P < 0.001), and lower e' septal (P < 0.001). CONCLUSIONS: CTRCD is an important concern among patients with active breast cancer, regardless of baseline risk factors, and is associated with trastuzumab and pertuzumab treatment. Early GLS evaluation may contribute to risk stratification and allow deployment of cardioprotective treatment.

Familial history of heart disease and increased risk for elevated troponin in apparently healthy individuals.

BACKGROUND: Family history of heart disease (FH-HD) is associated with an increase drisk of subsequent HD. High sensitive cardiac troponin T (hs-cTnT) is arecognized biomarker of myocyte injury even in HD free patients. We examined the association between FH-HD and hs-cTnT in apparently healthy individuals. HYPOTHESIS: FH-HD is associated with elevated hs-cTnT in apparently healthy individuals. METHODS: In a cross sectional study we analyzed data of apparently healthy individuals (n=3,821) recruited for the Tel-Aviv Medical Center Inflammation Survey (TAMCIS). Blood samples were obtained for hs-cTnT and high sensitive CRP (hs-CRP) among other tests. FH-HD was defined as first degree family member with HD diagnosis and classified as premature if the diagnosis was done before the age of 55 for men or 65 for women. RESULTS: Elevated hs-cTnT (>14 ng/L) was more common in FH-HD of any age, and in premature FH-HD (FH-P-HD) participants than in participants without FH-HD (4.4% vs 2.0%, p<0.001 and 4.3% vs 2.0%, p=0.001, respectively). Adjustmentfor potential risk factors with association to elevated hs-cTnT (age, sex, BMI, hypertension, diabetes, hs-CRP, smoking and physical activity), showed that FH-HD and FH-P-HD remained significantly associated with elevated hs-cTnT (OR=1.62, p=0.025 and OR=1.70, p=0.039, respectively). Furthermore, we found that a significant interaction between FH-HD or FH-P-HD and high levels ofhs-CRP (>3 mg/L) increased the risk for elevated hs-cTnT (OR=3.07, p=0.036 for FH-HD and OR=3.25, p=0.053 for FH-P-HD). CONCLUSIONS: FH-HD and its interaction with elevated hs-CRP levels were significantly associated with elevated hs-cTnT in apparently healthy individuals suggesting that an inflammatory process may be involved in this association.

C-reactive protein velocity and the risk of acute kidney injury among ST elevation myocardial infarction patients undergoing primary percutaneous intervention.

BACKGROUND: Elevated C-reactive protein (CRP) was shown to be associated with an increased risk for acute kidney injury (AKI) in ST elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI), however, the optimal time frame to measure CRP for risk stratification is not known. We evaluated the relation between the change in CRP over time (CRP velocity-CRPv) and AKI among STEMI patients treated with primary PCI. METHODS: We included 801 STEMI who presented between 2007 and 2017 and had their CRP measured with a wide range assay (wr-CRP) at least twice during the 24 h after admission. CRPv was defined as the change in wr-CRP concentration (mg/l) divided by the change in time (in h) between the two measurements. Patient's medical records were reviewed for occurrence of AKI. RESULTS: Mean age was 62 ± 16 and 80% were males. Patients with AKI had significantly higher CRPv (1.47 versus 0.4 mg/l/h, p < 0.001). In a multivariate regression model CRPv was independently associated with AKI (OR 1.03, 95% CI 1.01-1.0 5, p = 0.001). On receiver operating characteristic (ROC) curve the optimal cutoff value of CRPv to predict AKI was measured as more than 0.8 mg/l/h, with 70% sensitivity and 65% specificity (AUC 0.712, 95% CI 0.64-0.78, p < 0.001). CONCLUSION: CRPv might be an independent and rapidly measurable biomarker for AKI following primary PCI in STEMI patients.

Association of pre-admission statin therapy and the inflammatory response in ST elevation myocardial infarction patients.

PURPOSE: To demonstrate the possible association of statin therapy with C reactive protein (CRP) serial measurements in ST elevation myocardial infarction (STEMI) patients. MATERIALS AND METHODS: STEMI patients between 2008 and 2016 with available CRP data from admission were divided into two groups according to pre-admission statin therapy. A second CRP measurement was noted following primary coronary intervention (within 24 h from admission). The difference between the two measurements was designated ΔCRP. RESULTS: The cohort consisted of 1134 patients with a median age of 61 (IQR52-70), 81% males. Patients on statins prior to admission (336/1134, 26%) were more likely to have CRP levels within normal range (≤5 mg/l) compared to patients without prior treatment, both at admission (75 vs. 24%, p = 0.004) and at 24 h (70 vs. 48%, p = 0.029). The prevalence of patients with pre-admission statin therapy decreased as ΔCRP increased (p = 0.004; n = 301). The likelihood of ΔCRP to be above 5 mg/l in patients with pre-admission statin therapy was reduced after age and gender adjustments (OR 0.54, 95% CI 0.32-0.92, p = 0.023) and in multivariate (OR 0.57, 95% CI 0.33-0.99, p = 0.048) analysis. CONCLUSIONS: Pre-admission statin therapy is associated with a less robust inflammatory response in STEMI patients, highlighting statin's pathophysiological importance.