Citations

Abstract Background Cardiac sarcoidosis (CS) is an infiltrative inflammatory condition defined by infiltration of noncaseating granulomas into the heart. Based on the location of sarcoid lesion involvement, patients can present with symptoms of congestive heart failure, arrhythmias, and even sudden cardiac death. Purpose Diagnosis of CS has been somewhat challenging, with the Heart Rhythm Society (HRS) and Japanese Ministry of Health and Welfare (JMHW) being the 2 widely accepted diagnostic guidelines. Endomyocardial biopsy is the gold standard to prove definite CS but has a low sensitivity. Imaging studies have been helpful as non-invasive methods to diagnose probable CS but these can be logistically difficult and expensive. Thus, investigating for laboratory biomarkers that can act as both diagnostic and prognostic can be crucial in how we diagnose and manage CS in the future. Methods Patients meeting HRS for CS were evaluated at a single institution (n=217). Biomarkers of interest included angiotensin-converting enzyme (ACE), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), N-terminal pro B-type natriuretic peptide (NT-proBNP), troponin-T, 1,25 dihydroxyvitamin D (1,25-OHVit-D), and creatinine. Biomarkers were stratified by clinical variables of interest and their association with prognosis was examined. The primary endpoint was LVAD implantation, transplantation, or death. Results Mean values on presentation were: ACE 32.9±28, ESR 12±13, CRP 7.4±19, NT-proBNP 1630±2923, Troponin-T 0.03±0.1, 1,25-OHVit-D 55.5±20, and creatinine 1.12±0.3. None of the biomarkers differed by sex, definite or probable CS, or a history of immunosuppression. ACE levels were associated with the presence of cardiac fibrosis on cardiac MRI (mean difference 14.7, p=0.032). Troponin-T (p=0.006; HR 1.06 per 0.01 ng/mL), NT-proBNP (p=0.0003; HR 1.31 per 1,000 pg/mL), and creatinine (p=0.01; HR 4.02 per mg/dL) were each associated with the primary endpoint (52/217 patients). Biomarkers associated with long term outcomes in patients with cardiac sarcoidosis Biomarker Hazard ratio P value Troponin-T 1.06 (1.02–1.11)* 0.006 NT-pro BNP 1.31 (1.15–1.48)** 0.0003 Creatinine 4.02 (1.41–9.94)*** 0.01 *Per 0.01 ng/mL change; 99th percentile upper reference limit <0.01 ng/mL; **per 1,000 pg/mL change; ***per 1 mg/dL change. Conclusion Troponin-T, NT-proBNP, and creatinine at presentation predict outcomes in patients with CS. Further investigation on the utility of biomarkers for assessment of disease activity and treatment response is warranted.

Following implantation of continuous-flow left ventricular assist devices, mechanical off-loading results in improved resting hemodynamics; however, peak exercise capacity generally does not increase substantially. This study evaluated patients supported by continuous-flow left ventricular assist devices who were invasively monitored during exercise to define parameters that underpin exercise capacity and outcomes. A review of all patients supported by continuous-flow left ventricular assist devices who underwent supine bicycle ergometry exercise testing with measurement of pulmonary gas exchange during right heart catheterization for evaluation of dyspnea at one institution between 2007 and 2018 was performed (n = 22). The primary outcome of this investigation was death or heart failure hospitalization. Although resting filling pressures were relatively preserved, resting cardiac index (Fick) was low (2.1 ± 0.5 mL/kg/min). An impaired cardiac output reserve was present in 75% of patients. On univariate modeling, patients with supine exercise–induced hypoxemia (O 2 saturation <90%) experienced significantly diminished hospitalization-free survival (unadjusted hazard ratio = 11.0, confidence interval = 2.4–57.2, p = 0.003), which persisted despite adjustment for right heart catheterization peak VO 2 and peak cardiac output (adjusted hazard ratio = 25, confidence interval = 3.6–322, p = 0.001). Our findings suggest that supine exercise testing provides additional prognostic utility in the continuous-flow left ventricular assist device population.

Background Diastolic pulmonary gradient ( DPG ) was proposed as a better marker of pulmonary vascular remodeling compared with pulmonary vascular resistance ( PVR ) and transpulmonary gradient ( TPG ). The prognostic significance of DPG in patients requiring a left ventricular assist device ( LVAD ) remains unclear. We sought to investigate whether pre‐ LVAD DPG is a predictor of survival or right ventricular ( RV ) failure post‐ LVAD . Methods and Results We retrospectively reviewed 268 patients who underwent right heart catheterization before LVAD implantation from 2007 to 2017 and had pulmonary hypertension because of left heart disease. Patients were dichotomized using DPG ≥7 mm Hg, PVR ≥3 mm Hg, or TPG ≥12 mm Hg. The associations between these parameters and all‐cause mortality or RV failure post LVAD were assessed with Cox proportional hazards regression and Kaplan–Meier analyses. After a mean follow‐up time of 35 months, elevated DPG was associated with increased risk of RV failure (hazard ratio [ HR ]: 3.30; P =0.004, for DPG ≥7 versus DPG <7), whereas elevated PVR ( HR 1.85, P =0.13 for PVR ≥3 versus PVR <3) or TPG ( HR 1.47, P =0.35, for TPG ≥12 versus TPG <12) were not associated with the development of RV failure. Elevated DPG was not associated with mortality risk ( HR 1.16, P =0.54, for DPG ≥7 versus DPG <7), whereas elevated PVR , but not TPG , was associated with higher mortality risk ( HR 1.55; P =0.026, for PVR ≥3 versus PVR <3). Conclusions Among patients with pulmonary hypertension because of left heart disease requiring LVAD support, elevated DPG was associated with RV failure but not survival, while elevated PVR predicted mortality post LVAD implantation.

Background Left ventricular (LV) hemodynamic assessment has been sparsely performed in patients supported on continuous‐flow LV assist devices (cf LVADs ). Insight into dynamic changes of left heart parameters during ramp studies may improve LV assist device optimization and evaluate pathology. Methods and Results To complement right heart catheterization, a novel technique for left heart catheterization in patients with a cf LVAD was developed. Patients implanted with cf LVAD s underwent hemodynamic ramp left heart catheterization and right heart catheterization with transthoracic echocardiography. Continuous aortic and LV pressures were measured along with right atrial, pulmonary artery, and pulmonary capillary wedge pressures. A novel index, the transaortic gradient ( TAG ) was established. Thirty eight patients with cf LVADs were evaluated at a median of 446 days (interquartile range, 183–742) after device implant. During left heart catheterization performed for hemodynamic optimization, drop‐in LV end‐diastolic pressure and pulmonary capillary wedge pressure were associated with a rise in TAG . A range was identified for TAG (20–40 mm Hg) as providing the most optimal level of hemodynamic offloading. Pathologic states deviated from normal responses to ramp. LV assist device thrombosis was associated with an inability to increase in TAG during speed ramp. Significant aortic insufficiency was associated with a marked increase in LV end‐diastolic pressure despite a concomitant decrease in pulmonary capillary wedge pressure with increasing LV assist device speeds. Conclusions Inclusion of left heart catheterization to a typical right heart catheterization LV assist device ramp protocol imparted unique insights to optimize cf LVAD speeds in different clinical scenarios. A novel index, the TAG was defined and provided additional resolution to optimized offloading.

Background: Right ventricular systolic dysfunction (RVD) often coexists with various cardiopulmonary diseases. However, the association between RVD and risk of sudden cardiac death (SCD) has not been well studied. This study examined the risk of SCD associated with RVD in patients with heterogeneous underlying cardiac diseases. Methods: The Mayo Clinic cardiac care unit database included 5463 consecutive patients with complete echocardiographic evaluation to assess right ventricular systolic function and RVD severity. Prospective surveillance follow-up was obtained for all patients. SCD was adjudicated when a malignant ventricular arrhythmia was documented as the primary rhythm leading to death. RESULTS: The prevalence of mild RVD and moderate-severe RVD was 14.9% and 17.1%, respectively. Patients with RVD were more likely to have a history of congestive heart failure, cardiac arrest, pulmonary disease, and lower baseline left ventricular ejection fraction compared with those with normal right ventricular systolic function. During a median follow-up of 14 months, the incidence of SCD was highest in patients with moderate-severe RVD (7.4% versus 4.4% in mild RVD versus 1.6% in normal right ventricular function; P <0.001). After adjustment for baseline characteristics, mild RVD (adjusted hazard ratio, 1.57; P =0.046) and moderate-severe RVD (adjusted hazard ratio, 1.91; P =0.006) were independently associated with an increased risk of SCD. Moderate-severe RVD remained an independent predictor of SCD for patients with left ventricular ejection fraction >35% without or with preexisting implantable cardioverter-defibrillator (adjusted hazard ratio, 4.12; P =0.003 and adjusted hazard ratio, 5.04; P <0.001, respectively). Conclusions: Presence of RVD in patients with a history of preexisting cardiac disease is an independent predictor of SCD irrespective of left ventricular ejection fraction.

Background The true prevalence of heart failure due to wild type transthyretin amyloidosis (ATTRwt) is likely underestimated. There is a paucity of data with regard to the management of ATTRwt-related advanced heart failure and the natural history of extracardiac ATTRwt. Methods We conducted a retrospective cohort study of patients undergoing cardiac transplant (HTx) for ATTRwt at a single institution. Comprehensive clinical data, including baseline hemodynamic and echocardiographic characteristics, and posttransplant outcomes, were obtained. Results Seven patients with ATTRwt underwent HTx between 2007 and 2015. All patients were male with a mean age of 66 ± 9. Patients had a reduced ejection fraction (mean, 37 ± 14%) and elevated filling pressures pre-HTx (mean pulmonary capillary wedge pressure 22 ± 7 mm Hg) before HTx. Three-year survival was 100%; 1 patient died of pancreatic cancer 45 months post-HTx (1 death per 30.8 patient-years). Oxygen consumption (Δ +6.8 ± 4.9 mL·kg−1·min−1) and 6-minute walk distances (Δ +189 ± 60 m) improved. Symptomatic gastrointestinal involvement (n = 2) and peripheral nerve involvement (n = 4) by ATTRwt developed late. Conclusions This is the first report of a series of ATTRwt patients receiving HTx in which excellent outcomes are demonstrated. Although cardiac death is averted, systemic manifestations of ATTRwt may develop posttransplantation.

Although improvement in cardiac output and hemodynamic parameters is routinely demonstrated in patients implanted with continuous-flow left ventricular assist devices (CF-LVADs), improvement in exercise capacity is inconsistently seen. Our purpose was to determine whether native cardiac factors, LVAD factors, or comorbid factors were associated with lack of improvement. Review of all patients undergoing preimplant cardiopulmonary exercise testing (CPET) and CPET on LVAD therapy at one institution was performed between 2007 and 2014 (n = 49). Comprehensive assessment of echocardiographic parameters, right heart catheterization data, medications, and comorbid illness was undertaken. There was no mean improvement in peak oxygen consumption (VO2; 11.8–12.4 ml/kg/min; p = 0.26), although exercise time (5.1 [46% predicted] to 5.8 min [56% predicted]; p = 0.02) and nadir of the ratio of minute ventilation to carbon dioxide production slope (VE/VCO2; 39–36; p = 0.001) improved. Factors most strongly associated with improvement in VO2 were Heartmate II pulsatility index (PI; R = 0.48; p = 0.001), power (R = −0.40; p = 0.009), pump flow (R = −0.40; p = 0.008), and pump speed (R = −0.32; p = 0.04). Peak heart rate (HR) was also associated with improvement in VO2 (R = 0.41; p = 0.004). Left ventricular ejection fraction (LVEF; R = 0.004; p = 0.77), right ventricular (RV) function (R = 0.22; p = 0.28), and aortic valve opening (R = 0.20; p = 0.57) were not associated with improvement in VO2. Our data suggest that less reliance on LVAD support was modestly associated with improvement in exercise capacity. Further studies should seek to determine the optimal level of device support prospectively in relation to exercise capacity.

AbstractIntroductionCardiac pacing from the right ventricular apex is associated with detrimental long‐term effects and nonapical pacing locations may be associated with improved outcomes. There is little data regarding complications with nonapical lead positions. The aim of this study was to assess long‐term outcomes and lead‐related complications associated with differing ventricular lead tip position.Methods and resultsAll adult patients who underwent dual‐chamber pacemaker implantation from 2004 to 2014 were included if they had postprocedure chest radiographs amenable to lead position determination. Long‐term outcomes and lead‐related complication rates were recorded. These were compared at 5 years between: (1) apical and septal leads, (2) apical and nonseptal nonapical (NSNA), and (3) apical and septal with >40% ventricular pacing. We retrospectively evaluated 3,450 patients, which included 238 with a septal position and 733 with NSNA lead positions. Septal lead position was associated with a lower mortality compared to apical leads (24% vs. 31%, P = 0.02). In patients with greater than 40% pacing, septal leads were associated with significantly higher rates of incident atrial fibrillation compared to apical leads (49% vs. 34%, P = 0.04). NSNA positions were associated with a significantly higher rate of lead dislodgement (4% vs. 2%, P = 0.005) and need for revision (8% vs. 5%, P = 0.005).ConclusionsSeptal pacemaker lead position is associated with a lower mortality compared to apically placed leads, but a higher incidence of atrial fibrillation with higher percentage ventricular pacing. NSNA lead locations are associated with more complications and should be avoided.

Acute decompensated heart failure (ADHF) is a prominent condition whose frequency is increasing, especially in the context of an aging population. The ability to discern the cause of undifferentiated dyspnea in acute presentations is an increasing struggle. In this review, we seek to explore the various biomarkers that have been studied for the diagnosis of ADHF and their respective clinical utilities as the most recent data would suggest. Natriuretic peptides, galectin-3, soluble ST2, adrenomedullin, cardiac troponin-T, neutrophil gelatinase-associated lipocalin, and copeptin are reviewed. Of these biomarkers, natriuretic peptides are the most thoroughly evaluated and show the most promise for diagnosis or exclusion of acute heart failure, though other biomarkers can add significant utility in the form of prognostication.