scholarly journals Risk Stratification in Hypertrophic Cardiomyopathy. Insights from Genetic Analysis and Cardiopulmonary Exercise Testing

2020 ◽  
Vol 9 (6) ◽  
pp. 1636
Author(s):  
Damiano Magrì ◽  
Vittoria Mastromarino ◽  
Giovanna Gallo ◽  
Elisabetta Zachara ◽  
Federica Re ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Risk Stratification ◽  
Cardiac Troponin ◽  
Troponin I ◽  
Troponin T ◽  
Cardiopulmonary Exercise Testing ◽  
Peak Oxygen Uptake ◽  
Variant Of Uncertain Significance ◽  
Cardiopulmonary Exercise

The role of genetic testing over the clinical and functional variables, including data from the cardiopulmonary exercise test (CPET), in the hypertrophic cardiomyopathy (HCM) risk stratification remains unclear. A retrospective genotype–phenotype correlation was performed to analyze possible differences between patients with and without likely pathogenic/pathogenic (LP/P) variants. A total of 371 HCM patients were screened at least for the main sarcomeric genes MYBPC3 (myosin binding protein C), MYH7 (β-myosin heavy chain), TNNI3 (cardiac troponin I) and TNNT2 (cardiac troponin T): 203 patients had at least an LP/P variant, 23 patients had a unique variant of uncertain significance (VUS) and 145 did not show any LP/P variant or VUS. During a median 5.4 years follow-up, 51 and 14 patients developed heart failure (HF) and sudden cardiac death (SCD) or SCD-equivalents events, respectively. The LP/P variant was associated with a more aggressive HCM phenotype. However, left atrial diameter (LAd), circulatory power (peak oxygen uptake*peak systolic blood pressure, CP%) and ventilatory efficiency (C-index = 0.839) were the only independent predictors of HF whereas only LAd and CP% were predictors of the SCD end-point (C-index = 0.738). The present study reaffirms the pivotal role of the clinical variables and, particularly of those CPET-derived, in the HCM risk stratification.

Risk stratification in hf with mid-range LVEF: the role of cardiopulmonary exercise testing

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
B.M.L Rocha ◽  
G.J Lopes Da Cunha ◽  
P.M.D Lopes ◽  
P.N Freitas ◽  
F Gama ◽  
...  
Keyword(s):  
Risk Stratification ◽  
Exercise Testing ◽  
Primary Endpoint ◽  
Prognostic Significance ◽  
Cardiopulmonary Exercise Testing ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Cardiopulmonary Exercise

Abstract Background Cardiopulmonary exercise testing (CPET) is recommended in the evaluation of selected patients with Heart Failure (HF). Notwithstanding, its prognostic significance has mainly been ascertained in those with left ventricular ejection fraction (LVEF) <40% (i.e., HFrEF). The main goal of our study was to assess the role of CPET in risk stratification of HF with mid-range (40–49%) LVEF (i.e., HFmrEF) compared to HFrEF. Methods We conducted a single-center retrospective study of consecutive patients with HF and LVEF <50% who underwent CPET from 2003–2018. The primary composite endpoint of death, heart transplant or HF hospitalization was assessed. Results Overall, 404 HF patients (mean age 57±11 years, 78.2% male, 55.4% ischemic HF) were included, of whom 321 (79.5%) had HFrEF and 83 (20.5%) HFmrEF. Compared to the former, those with HFmrEF had a significantly higher mean peak oxygen uptake (pVO2) (20.2±6.1 vs 16.1±5.0 mL/kg/min; p<0.001), lower median minute ventilation/carbon dioxide production (VE/VCO2) [35.0 (IQR: 29.1–41.2) vs 39.0 (IQR: 32.0–47.0); p=0.002) and fewer patients with exercise oscillatory ventilation (EOV) (22.0 vs 46.3%; p<0.001). Over a median follow-up of 28.7 (IQR: 13.0–92.3) months, 117 (28.9%) patients died, 53 (13.1%) underwent heart transplantation, and 134 (33.2%) had at least one HF hospitalization. In both HFmrEF and HFrEF, pVO2 <12 mL/kg/min, VE/VCO2 >35 and EOV identified patients at higher risk for events (all p<0.05). In Cox regression multivariate analysis, pVO2 was predictive of the primary endpoint in both HFmrEF and HFrEF (HR per +1 mL/kg/min: 0.81; CI: 0.72–0.92; p=0.001; and HR per +1 mL/kg/min: 0.92; CI: 0.87–0.97; p=0.004), as was EOV (HR: 4.79; CI: 1.41–16.39; p=0.012; and HR: 2.15; CI: 1.51–3.07; p<0.001). VE/VCO2, on the other hand, was predictive of events in HFrEF but not in HFmrEF (HR per unit: 1.03; CI: 1.02–1.05; p<0.001; and HR per unit: 0.99; CI: 0.95–1.03; p=0.512, respectively). ROC curve analysis demonstrated that a pVO2 >16.7 and >15.8 mL/kg/min more accurately identified patients at lower risk for the primary endpoint (NPV: 91.2 and 60.5% for HFmrEF and HFrEF, respectively; both p<0.001). Conclusions CPET is a useful tool in HFmrEF. Both pVO2 and EOV independently predicted the primary endpoint in HFmrEF and HFrEF, contrasting with VE/VCO2, which remained predictive only in latter group. Our findings strengthen the prognostic role of CPET in HF with either reduced or mid-range LVEF. Funding Acknowledgement Type of funding source: None

Reply: The complementary role of cardiac troponin I and cardiac troponin T

2020 ◽  
Vol 78 ◽  
pp. 42
Author(s):  
Sjur H. Tveit ◽  
Peder L. Myhre ◽  
Helge Røsjø ◽  
Torbjørn Omland
Keyword(s):  
Cardiac Troponin ◽  
Troponin I ◽  
Troponin T ◽  
Cardiac Troponin I ◽  
Cardiac Troponin T ◽  
Complementary Role

Kinetics of high-sensitivity cardiac troponin T or troponin I compared to creatine kinase in patients with revascularized acute myocardial infarction

2015 ◽  
Vol 53 (5) ◽  
Author(s):  
Kamila Solecki ◽  
Anne Marie Dupuy ◽  
Nils Kuster ◽  
Florence Leclercq ◽  
Richard Gervasoni ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Cardiac Troponin ◽  
Troponin I ◽  
Troponin T ◽  
High Sensitivity ◽  
Cardiac Troponin T ◽  
Significant Difference ◽  
Kinetics Of

AbstractCardiac biomarkers are the cornerstone of the biological definition of acute myocardial infarction (AMI). The key role of troponins in diagnosis of AMI is well established. Moreover, kinetics of troponin I (cTnI) and creatine kinase (CK) after AMI are correlated to the prognosis. New technical assessment like high-sensitivity cardiac troponin T (hs-cTnT) raises concerns because of its unclear kinetic following the peak. This study aims to compare kinetics of cTnI and hs-cTnT to CK in patients with large AMI successfully treated by percutaneous coronary intervention (PCI).We prospectively studied 62 patients with anterior AMI successfully reperfused with primary angioplasty. We evaluated two consecutive groups: the first one regularly assessed by both CK and cTnI methods and the second group by CK and hs-cTnT. Modeling of kinetics was realized using mixed effects with cubic splines.Kinetics of markers showed a peak at 7.9 h for CK, at 10.9 h (6.9–12.75) for cTnI and at 12 h for hs-cTnT. This peak was followed by a nearly log linear decrease for cTnI and CK by contrast to hs-cTnT which appeared with a biphasic shape curve marked by a second peak at 82 h. There was no significant difference between the decrease of cTnI and CK (p=0.63). CK fell by 79.5% (76.1–99.9) vs. cTnI by 86.8% (76.6–92.7). In the hs-cTnT group there was a significant difference in the decrease by 26.5% (9–42.9) when compared with CK that fell by 79.5% (64.3–90.7).Kinetic of hs-cTnT and not cTnI differs from CK. The role of hs-cTnT in prognosis has to be investigated.

Cardiopulmonary exercise testing in patients undergoing radical cystectomy (open, laparoscopic and robotic)

2014 ◽  
Vol 7 (6) ◽  
pp. 374-379 ◽  
Author(s):  
Kimberley Hoyland ◽  
Nikhil Vasdev ◽  
James M Adshead ◽  
Andrew Thorpe
Keyword(s):  
Risk Stratification ◽  
Radical Cystectomy ◽  
Exercise Testing ◽  
Functional Assessment ◽  
Postoperative Care ◽  
Assessment Tool ◽  
Cardiopulmonary Exercise Testing ◽  
Cardiopulmonary Exercise

The use of cardiopulmonary exercise testing (CPET) is gaining popularity as a preoperative functional assessment tool and is a useful adjunct to risk stratification before radical cystectomy. It is important for urologists to understand the indications, contraindications, methodology and different parameters evaluated during CPET assessment and use this information acquired to tailor pre-, intra- and postoperative care in patients undergoing a radical cystectomy. We present a review on the increasing role of CPET in patients undergoing a radical cystectomy.

scholarly journals Risk stratification and survival in patients with HFmrEF: the role of cardiopulmonary exercise testing

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
J.G Westphal ◽  
P.C Schulze
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Risk Stratification ◽  
Exercise Testing ◽  
Primary Endpoint ◽  
Cardiopulmonary Exercise Testing ◽  
Cardiopulmonary Exercise ◽  
All Cause Mortality

Abstract Background The prognostic value of cardiopulmonary exercise testing (CPET) is established for risk stratification in patients with heart failure (HF) and reduced ejection fraction (HFrEF). Since the introduction of HF with mid-range ejection fraction (HFmrEF) as an additional category in 2016, optimal management strategy and risk stratification for these patients is a field of ongoing research. Purpose Left ventricular ejection fraction (LVEF) is only one part of the picture when planning treatment and estimating long time risk for patients with HF. We planned to investigate the predictive long-term value of exercise intolerance as measured by CPET in patients with HFmrEF in comparison to HFrEF. Methods We performed a single-center retrospective cohort study of ambulatory consecutive patients that showed signs of heart failure (NYHA functional class II or III) and had a LVEF of 49% or below as measured by echocardiography at the time of CPET. All patients underwent CPET evaluation with an upright bicycle between 2015–2017. The primary endpoint of all-cause mortality as well as the secondary composite endpoint of all-cause mortality or heart transplant/ventricular assist device implantation (transplant/VAD free survival) were assessed. Results For the primary analysis, 253 patients (mean age 61.2±13.0 years, 82.6% male) were included. 68 patients showed an LVEF between 40 and 49% (HFmrEF) whereas 185 patients had an LVEF of below 40% (HFrEF). HF etiology was in 31.3% ischemic. Mean BNP values were 788±1061 pg/ml while HFmrEF patients had on average lower values than HFrEF (322±676 vs. 945±1121, p<0.001). Patients were followed up for a median of 4.2 years (IQR: 3.5–5.0 years). Over this period, the primary and secondary end-point occurred in 22.5%/30.8% of patients. Patients in the HFmrEF group showed a higher mean peak oxygen uptake compared to HFrEF (pVO2; 17.3±4.6 vs 14.2±3.7 ml/min/kg, p<0.001), peak exercise power (Pmax; 111±49 vs 91±38 Watt, p=0.02) and peak oxygen pulse (pO2/HR; 12.6±4.2 vs 10.4±4.1 ml/min/kg, p<0.001). The Kaplan-Meier-Estimate showed a significant difference in survival for both HFmrEF and HFrEF who had pVO2 below 14 ml/min/kg (Log Rank: Chi2: 4.45, p=0.035 and Chi2: 10.05, p=0.02). In univariate Cox regression, pVO2 was predictive of the primary endpoint (HR per +1 mL/kg/min: 0.81; CI: 0.71–0.93; p=0.002 and HR per +1 mL/kg/min: 0.84; CI: 0.77–0.92; p<0.001) in both groups as was Pmax and pO2/HR (p<0.05 for both variables in both groups). Conclusion As in HFrEF, CPET is a useful tool to stratify risk in HFmrEF as well. Our findings support the prognostic role of pVO2 as well as pO2/HR and Pmax in HF with mid-range LVEF. Using a cut off of pVO2 14 ml/min/kg selected patients at risk with similar long-term prognosis as in the HFrEF cohort. Further research to identify subgroups at risk within the heterogeneous group of HFmrEF is warranted for optimal risk stratification. FUNDunding Acknowledgement Type of funding sources: None.

scholarly journals The role of cardiac troponin t and other new biochemical markers in evaluation and risk stratification of patients with acute chest pain syndromes

1997 ◽  
Vol 20 (11) ◽  
pp. 934-942 ◽  
Author(s):  
B. Charles Solymoss ◽  
Martial G. Bourassa ◽  
Ewa Wesolowska ◽  
Ihor Dryda ◽  
Pierre Th$Earoux ◽  
...  
Keyword(s):  
Chest Pain ◽  
Risk Stratification ◽  
Cardiac Troponin ◽  
Biochemical Markers ◽  
Troponin T ◽  
Acute Chest Pain ◽  
Cardiac Troponin T ◽  
Pain Syndromes

scholarly journals Mavacamten rescues increased myofilament calcium sensitivity and dysregulation of Ca2+ flux caused by thin filament hypertrophic cardiomyopathy mutations

2020 ◽  
Vol 318 (3) ◽  
pp. H715-H722 ◽  
Author(s):  
Alexander J. Sparrow ◽  
Hugh Watkins ◽  
Matthew J. Daniels ◽  
Charles Redwood ◽  
Paul Robinson
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Cardiac Troponin ◽  
Thin Filament ◽  
Troponin I ◽  
Troponin T ◽  
Thick Filament ◽  
Calcium Sensitivity ◽  
Calcium Handling ◽  
Cellular Models

Thin filament hypertrophic cardiomyopathy (HCM) mutations increase myofilament Ca2+ sensitivity and alter Ca2+ handling and buffering. The myosin inhibitor mavacamten reverses the increased contractility caused by HCM thick filament mutations, and we here test its effect on HCM thin filament mutations where the mode of action is not known. Mavacamten (250 nM) partially reversed the increased Ca2+ sensitivity caused by HCM mutations Cardiac troponin T (cTnT) R92Q, and cardiac troponin I (cTnI) R145G in in vitro ATPase assays. The effect of mavacamten was also analyzed in cardiomyocyte models of cTnT R92Q and cTnI R145G containing cytoplasmic and myofilament specific Ca2+ sensors. While mavacamten rescued the hypercontracted basal sarcomere length, the reduced fractional shortening did not improve with mavacamten. Both mutations caused an increase in peak systolic Ca2+ detected at the myofilament, and this was completely rescued by 250 nM mavacamten. Systolic Ca2+ detected by the cytoplasmic sensor was also reduced by mavacamten treatment, although only R145G increased cytoplasmic Ca2+. There was also a reversal of Ca2+ decay time prolongation caused by both mutations at the myofilament but not in the cytoplasm. We thus show that mavacamten reverses some of the Ca2+-sensitive molecular and cellular changes caused by the HCM mutations, particularly altered Ca2+ flux at the myofilament. The reduction of peak systolic Ca2+ as a consequence of mavacamten treatment represents a novel mechanism by which the compound is able to reduce contractility, working synergistically with its direct effect on the myosin motor. NEW & NOTEWORTHY Mavacamten, a myosin inhibitor, is currently in phase-3 clinical trials as a pharmacotherapy for hypertrophic cardiomyopathy (HCM). Its efficacy in HCM caused by mutations in thin filament proteins is not known. We show in reductionist and cellular models that mavacamten can rescue the effects of thin filament mutations on calcium sensitivity and calcium handling although it only partially rescues the contractile cellular phenotype and, in some cases, exacerbates the effect of the mutation.

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