Different clinical characteristics and outcomes of hypertrophic cardiomyopathy with and without hypertension: seeking the truth.

OBJECTIVE:To determine the different clinical characteristics and outcomes of hypertrophic cardiomyopathy (HCM) patients with and without hypertension (HT).METHODS:A total of 696 HCM patients were included in this study and all HCM diagnoses were confirmed by the genetic test. Patients were analyzed separately in the septal reduction therapy (SRT) cohort and the non-SRT cohort. The primary endpoint was cardiovascular death and the secondary endpoint was all-cause death. Outcome analyses were conducted to evaluate the associations between HT and outcomes in HCM. Medications before enrollment and at discharge were collected in the post-hoc analyses.RESULTS:HCM patients without HT were younger, had a lower body mass index, were more likely to have a family history of HCM, and had a smaller left ventricular (LV) end-diastolic diameter than those with HT in both cohorts. A thicker LV wall, a higher level of N-terminal pro-B-type natriuretic peptide, and a higher extent of LV late gadolinium enhancement were additionally observed in patients without HT in the non-SRT cohort. The presence of HT did not alter the distribution pattern of late gadolinium enhancement, as well as the constituent ratio of eight disease-causing sarcomeric gene variants in both cohorts. Outcome analyses showed that in the non-SRT cohort, patients without HT had higher risks of cardiovascular death (HR = 2.537, P = 0.032) and all-cause death (HR = 3.309, P = 0.032). While such prognostic divergence was not observed in the SRT cohort. Further post-hoc analyses in the non-SRT cohort found that patients without HT received fewer non-dihydropyridine calcium channel blockers and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers before enrollment and at discharge.CONCLUSIONS:HCM patients without HT had worse clinical conditions and higher mortality than patients with HT overall, which may result from active medical therapy in HT patients. Active SRT may have a substantial de-risking effect on patients meeting the indications.

Cardiac index: A superior parameter of cardiac function than left ventricular ejection fraction in risk stratification of hypertrophic cardiomyopathy.

BACKGROUND:An appropriate indicator of cardiac function in the risk stratification of hypertrophic cardiomyopathy (HCM) patients is urgently needed. Cardiac index that reflects cardiac pumping function may be suitable.OBJECTIVE:The purpose of this study was to investigate the clinical significance of reduced cardiac index in HCM patients.METHODS:A total of 927 HCM patients were enrolled. The primary endpoint was cardiovascular death. The secondary endpoints were sudden cardiac death (SCD) and all-cause death. Combination models were constructed by adding reduced cardiac index and reduced left ventricular ejection fraction (LVEF) to the HCM risk-SCD model. Predictive accuracy was determined by C-statistics.RESULTS:Reduced cardiac index was defined as cardiac index ≤2.42 L/min/m2. During median follow-up of 4.3 years, 51 patients reached the endpoint. Reduced cardiac index independently increased the risk of cardiovascular death (adjusted hazard ratio [aHR] 2.976; P = .007), SCD (aHR 6.385; P = .001), and all-cause death (aHR 2.428; P = .010). By adding reduced cardiac index to the HCM risk-SCD model, the model C-statistic increased from 0.691 to 0.762, with an integrated discrimination improvement of 0.021 (P = .018) and a net reclassification improvement of 0.560 (P = .007). The addition of reduced LVEF failed to improve the original model. Better predictive accuracy for all endpoints was also indicated in reduced cardiac index than in reduced LVEF.CONCLUSION:Reduced cardiac index is an independent predictor of poor prognoses in HCM patients. Combining reduced cardiac index rather than reduced LVEF improved the HCM risk-SCD stratification strategy. The reduced cardiac index showed better predictive accuracy than reduced LVEF for all endpoints.

Implications of structural right ventricular involvement in patients with hypertrophic cardiomyopathy.

AIMS:In the clinical practice, the right ventricular (RV) manifestations have received less attention in hypertrophic cardiomyopathy (HCM). This paper aimed to evaluate the risk prediction value and genetic characteristics of RV involvement in HCM patients.METHODS AND RESULTS:A total of 893 patients with HCM were recruited. RV hypertrophy, RV obstruction, and RV late gadolinium enhancement were evaluated by echocardiography and/or cardiac magnetic resonance. Patients with any of the above structural abnormalities were identified as having RV involvement. All patients were followed with a median follow-up time of 3.0 years. The primary endpoint was cardiovascular death; the secondary endpoints were all-cause death and heart failure (HF)-related death. Survival analyses were conducted to evaluate the associations between RV involvement and the endpoints. Genetic testing was performed on 669 patients. RV involvement was recognized in 114 of 893 patients (12.8%). Survival analyses demonstrated that RV involvement was an independent risk factor for cardiovascular death (P = 0.002), all-cause death (P = 0.011), and HF-related death (P = 0.004). These outcome results were then confirmed by a sensitivity analysis. Genetic testing revealed a higher frequency of genotype-positive in patients with RV involvement (57.0% vs. 31.0%, P < 0.001), and the P/LP variants of MYBPC3 were more frequently identified in patients with RV involvement (30.4% vs. 12.0%, P < 0.001). Logistic analyses indicated the independent correlation between RV involvement and these genetic factors.CONCLUSION:RV involvement was an independent risk factor for cardiovascular death, all-cause death and HF-related death in HCM patients. Genetic factors might contribute to RV involvement in HCM.

Identification of heart failure with preserved ejection fraction helps risk stratification for hypertrophic cardiomyopathy.

BACKGROUND:Heart failure with preserved ejection fraction (HFpEF) is the dominant form of heart failure (HF). We here aimed to investigate the characteristics and prognosis of HFpEF in patients with hypertrophic cardiomyopathy (HCM).METHODS:This was a prospective cohort study and patients with HCM with available NT-proBNP results were enrolled. Patients were categorized into HFpEF [defined as LVEF ≥50%, with symptoms or signs of HF, and N-terminal pro-brain natriuretic peptide ≥800 pg/mL according to American Heart Association (AHA) criteria] and without heart failure (non-HF). The outcomes of interest were all-cause death, cardiovascular death, and sudden cardiac death (SCD).RESULTS:Of 1178 included patients with HCM, 513 (43.5%) were identified as having HFpEF according to AHA criteria. Compared with non-HF patients, patients with HFpEF had significantly larger maximal wall thickness (P < 0.001), higher maximal left ventricular outflow tract gradient (P < 0.001), higher proportion of atrial fibrillation (P < 0.001), higher incidence of all-cause death (log-rank test, P = 0.002), and cardiovascular death (log-rank test, P = 0.005). Multivariable Cox analysis showed that patients with HFpEF had a nearly two-fold higher risk of all-cause death (adjusted HR = 1.80, 95% CI 1.11-2.90; P = 0.017) and cardiovascular death (adjusted HR =1.82, 95% CI 1.05-3.18; P = 0.033) than non-HF patients.CONCLUSIONS:Patients with HCM have a high prevalence of HFpEF and those with HFpEF present greater disease severity and higher mortality than non-HF patients, and thus may require an appropriate and more aggressive treatment for HF management. Identification of patients with HFpEF using AHA criteria can provide guidance on patient risk stratification for patients with HCM.

[A case of wild-type transthyretin cardiac amyloidosis].

Truncating Variants in OBSCN Gene Associated With Disease-Onset and Outcomes of Hypertrophic Cardiomyopathy.

BACKGROUND:The presence of variants in OBSCN was identified to be linked to hypertrophic cardiomyopathy (HCM), but whether OBSCN truncating variants were associated with HCM remained unknown.METHODS:Whole-exome sequencing was performed in 986 patients with HCM and 761 non-HCM controls to search for OBSCN truncating variants, and the result was tested in a replication cohort consisting of 529 patients with HCM and 307 controls. The association of the OBSCN truncating variants with baseline characteristics and prognosis of patients with HCM were ascertained.RESULTS:There were 28 qualifying truncating variants in the OBSCN gene detected in 26 (2.6%) patients with HCM and 6 (0.8%) controls. The OBSCN truncating variants were more prevalent in patients with HCM than controls (odds ratio, 3.4, P=0.004). This association was confirmed in the replication cohort (odds ratio, 3.8, P=0.024). The combined effects of the two cohorts estimated the odds ratio to be 3.58 (P<0.001). Patients with or without OBSCN truncating variants shared similar demographic and echocardiographic variables at baseline. During 3.3±2.4 years (4795 patient-years) follow-up, the patients with OBSCN truncating variants were more likely to experience cardiovascular death (adjusted hazard ratio, 3.1 [95% CI, 1.40-6.70], P=0.005) and all-cause death (adjusted hazard ratio, 2.63 [95% CI, 1.21-5.71], P=0.015).CONCLUSIONS:Our data indicated that OBSCN truncating variants contributed to the disease-onset of HCM, and increased the risk of malignant events in patients with HCM.

[Incidence of coronary artery disease and outcome of patients with left ventricular noncompaction].

OBJECTIVE:To analyze the incidence of coronary artery disease (CAD) and outcome of patients with left ventricular noncompaction (LVNC).METHODS:Fifty-one patients with LVNC evaluated by echocardiography and/or cardiac magnetic resonance (CMR) from January 2006 to August 2010 were retrospectively reviewed. Coronary angiography or MDCT was performed for detecting coronary artery disease. Predictors of the cardiac events were analyzed by Cox regression analysis.RESULTS:There were 31 LVNC patients without CAD and 20 LVNC patients with CAD including single vessel coronary disease in 9 cases, double vessel coronary disease in 3 cases, three vessel coronary disease in 5 cases and left main coronary disease in 3 cases. Coronary artery bypass graft and percutaneous coronary intervention (PCI) were performed in 4 patients. Compared to LVNC patients without CAD, mean age (P = 0.008), incidence of hypertension (65.0% vs. 19.4%, P = 0.001), diabetes mellitus (40.0% vs. 12.9%, P = 0.026) and hyperlipidemia (55.0% vs. 25.8%, P = 0.035) were significantly higher while NT-proBNP level was significantly lower (P = 0.049) in LVNC patients with CAD. Incidence of major cardiac events was similar in LVNC patients with or without CAD. LogNT-proBNP is the independent prognostic factor for adverse cardiac events in patients with LVNC (HR 3.993, 95%CI 1.140 - 13.988, P = 0.030).CONCLUSIONS:Coronary artery disease is common in patients with LVNC and associated with traditional risk factors for CAD. Poor prognosis is associated with increased NT-proBNP but not with CAD in this patient cohort.

Does NT-proBNP remain a sensitive biomarker for chronic heart failure after administration of a beta-blocker?

BACKGROUND:Beta-blockers exert complex effects on plasma N-terminal-pro-B-type natriuretic peptide (NT-proBNP) level.HYPOTHESIS:We aimed to investigate whether NT-proBNP was still able to mirror the severity of chronic heart failure and predict the prognosis of the disease after administration of a beta-blocker.METHODS:Forty-four patients with chronic congestive heart failure were enrolled in the study to randomly receive carvedilol or bisoprolol in addition to background therapy. These patients underwent clinical measurement and blood sampling for NT-proBNP measurement at baseline and 3 or 7 months after the addition of the beta-blocker. The patients were followed-up for 3 years in order to register the occurrence of all-cause death.RESULTS:NT-proBNP level showed a positive correlation with the severity of heart failure as evaluated by New York Heart Association (NYHA) classification both before and after administration of either beta-blocker. The relationship between NT-proBNP and NYHA class was not weakened with the duration of therapy. Furthermore, NT-proBNP was the only independent predictor of all-cause mortality both before and after administration of either beta-blocker. Left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter (LVEDD), age, NYHA class and treatment group were not independently predictive of mortality in this study.CONCLUSIONS:The ability of NT-proBNP to reflect the severity and to predict the endpoint in chronic heart failure is not undermined after administration of a beta-blocker, suggesting that NT-proBNP remains a sensitive biomarker for chronic heart failure both before and after administration of a beta-blocker.

Different clinical characteristics and outcomes of hypertrophic cardiomyopathy with and without hypertension: seeking the truth.

OBJECTIVE:To determine the different clinical characteristics and outcomes of hypertrophic cardiomyopathy (HCM) patients with and without hypertension (HT).METHODS:A total of 696 HCM patients were included in this study and all HCM diagnoses were confirmed by the genetic test. Patients were analyzed separately in the septal reduction therapy (SRT) cohort and the non-SRT cohort. The primary endpoint was cardiovascular death and the secondary endpoint was all-cause death. Outcome analyses were conducted to evaluate the associations between HT and outcomes in HCM. Medications before enrollment and at discharge were collected in the post-hoc analyses.RESULTS:HCM patients without HT were younger, had a lower body mass index, were more likely to have a family history of HCM, and had a smaller left ventricular (LV) end-diastolic diameter than those with HT in both cohorts. A thicker LV wall, a higher level of N-terminal pro-B-type natriuretic peptide, and a higher extent of LV late gadolinium enhancement were additionally observed in patients without HT in the non-SRT cohort. The presence of HT did not alter the distribution pattern of late gadolinium enhancement, as well as the constituent ratio of eight disease-causing sarcomeric gene variants in both cohorts. Outcome analyses showed that in the non-SRT cohort, patients without HT had higher risks of cardiovascular death (HR = 2.537, P = 0.032) and all-cause death (HR = 3.309, P = 0.032). While such prognostic divergence was not observed in the SRT cohort. Further post-hoc analyses in the non-SRT cohort found that patients without HT received fewer non-dihydropyridine calcium channel blockers and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers before enrollment and at discharge.CONCLUSIONS:HCM patients without HT had worse clinical conditions and higher mortality than patients with HT overall, which may result from active medical therapy in HT patients. Active SRT may have a substantial de-risking effect on patients meeting the indications.

Cardiac index: A superior parameter of cardiac function than left ventricular ejection fraction in risk stratification of hypertrophic cardiomyopathy.

BACKGROUND:An appropriate indicator of cardiac function in the risk stratification of hypertrophic cardiomyopathy (HCM) patients is urgently needed. Cardiac index that reflects cardiac pumping function may be suitable.OBJECTIVE:The purpose of this study was to investigate the clinical significance of reduced cardiac index in HCM patients.METHODS:A total of 927 HCM patients were enrolled. The primary endpoint was cardiovascular death. The secondary endpoints were sudden cardiac death (SCD) and all-cause death. Combination models were constructed by adding reduced cardiac index and reduced left ventricular ejection fraction (LVEF) to the HCM risk-SCD model. Predictive accuracy was determined by C-statistics.RESULTS:Reduced cardiac index was defined as cardiac index ≤2.42 L/min/m2. During median follow-up of 4.3 years, 51 patients reached the endpoint. Reduced cardiac index independently increased the risk of cardiovascular death (adjusted hazard ratio [aHR] 2.976; P = .007), SCD (aHR 6.385; P = .001), and all-cause death (aHR 2.428; P = .010). By adding reduced cardiac index to the HCM risk-SCD model, the model C-statistic increased from 0.691 to 0.762, with an integrated discrimination improvement of 0.021 (P = .018) and a net reclassification improvement of 0.560 (P = .007). The addition of reduced LVEF failed to improve the original model. Better predictive accuracy for all endpoints was also indicated in reduced cardiac index than in reduced LVEF.CONCLUSION:Reduced cardiac index is an independent predictor of poor prognoses in HCM patients. Combining reduced cardiac index rather than reduced LVEF improved the HCM risk-SCD stratification strategy. The reduced cardiac index showed better predictive accuracy than reduced LVEF for all endpoints.

Implications of structural right ventricular involvement in patients with hypertrophic cardiomyopathy.

AIMS:In the clinical practice, the right ventricular (RV) manifestations have received less attention in hypertrophic cardiomyopathy (HCM). This paper aimed to evaluate the risk prediction value and genetic characteristics of RV involvement in HCM patients.METHODS AND RESULTS:A total of 893 patients with HCM were recruited. RV hypertrophy, RV obstruction, and RV late gadolinium enhancement were evaluated by echocardiography and/or cardiac magnetic resonance. Patients with any of the above structural abnormalities were identified as having RV involvement. All patients were followed with a median follow-up time of 3.0 years. The primary endpoint was cardiovascular death; the secondary endpoints were all-cause death and heart failure (HF)-related death. Survival analyses were conducted to evaluate the associations between RV involvement and the endpoints. Genetic testing was performed on 669 patients. RV involvement was recognized in 114 of 893 patients (12.8%). Survival analyses demonstrated that RV involvement was an independent risk factor for cardiovascular death (P = 0.002), all-cause death (P = 0.011), and HF-related death (P = 0.004). These outcome results were then confirmed by a sensitivity analysis. Genetic testing revealed a higher frequency of genotype-positive in patients with RV involvement (57.0% vs. 31.0%, P < 0.001), and the P/LP variants of MYBPC3 were more frequently identified in patients with RV involvement (30.4% vs. 12.0%, P < 0.001). Logistic analyses indicated the independent correlation between RV involvement and these genetic factors.CONCLUSION:RV involvement was an independent risk factor for cardiovascular death, all-cause death and HF-related death in HCM patients. Genetic factors might contribute to RV involvement in HCM.

Identification of heart failure with preserved ejection fraction helps risk stratification for hypertrophic cardiomyopathy.

BACKGROUND:Heart failure with preserved ejection fraction (HFpEF) is the dominant form of heart failure (HF). We here aimed to investigate the characteristics and prognosis of HFpEF in patients with hypertrophic cardiomyopathy (HCM).METHODS:This was a prospective cohort study and patients with HCM with available NT-proBNP results were enrolled. Patients were categorized into HFpEF [defined as LVEF ≥50%, with symptoms or signs of HF, and N-terminal pro-brain natriuretic peptide ≥800 pg/mL according to American Heart Association (AHA) criteria] and without heart failure (non-HF). The outcomes of interest were all-cause death, cardiovascular death, and sudden cardiac death (SCD).RESULTS:Of 1178 included patients with HCM, 513 (43.5%) were identified as having HFpEF according to AHA criteria. Compared with non-HF patients, patients with HFpEF had significantly larger maximal wall thickness (P < 0.001), higher maximal left ventricular outflow tract gradient (P < 0.001), higher proportion of atrial fibrillation (P < 0.001), higher incidence of all-cause death (log-rank test, P = 0.002), and cardiovascular death (log-rank test, P = 0.005). Multivariable Cox analysis showed that patients with HFpEF had a nearly two-fold higher risk of all-cause death (adjusted HR = 1.80, 95% CI 1.11-2.90; P = 0.017) and cardiovascular death (adjusted HR =1.82, 95% CI 1.05-3.18; P = 0.033) than non-HF patients.CONCLUSIONS:Patients with HCM have a high prevalence of HFpEF and those with HFpEF present greater disease severity and higher mortality than non-HF patients, and thus may require an appropriate and more aggressive treatment for HF management. Identification of patients with HFpEF using AHA criteria can provide guidance on patient risk stratification for patients with HCM.

[A case of wild-type transthyretin cardiac amyloidosis].

Truncating Variants in OBSCN Gene Associated With Disease-Onset and Outcomes of Hypertrophic Cardiomyopathy.

BACKGROUND:The presence of variants in OBSCN was identified to be linked to hypertrophic cardiomyopathy (HCM), but whether OBSCN truncating variants were associated with HCM remained unknown.METHODS:Whole-exome sequencing was performed in 986 patients with HCM and 761 non-HCM controls to search for OBSCN truncating variants, and the result was tested in a replication cohort consisting of 529 patients with HCM and 307 controls. The association of the OBSCN truncating variants with baseline characteristics and prognosis of patients with HCM were ascertained.RESULTS:There were 28 qualifying truncating variants in the OBSCN gene detected in 26 (2.6%) patients with HCM and 6 (0.8%) controls. The OBSCN truncating variants were more prevalent in patients with HCM than controls (odds ratio, 3.4, P=0.004). This association was confirmed in the replication cohort (odds ratio, 3.8, P=0.024). The combined effects of the two cohorts estimated the odds ratio to be 3.58 (P<0.001). Patients with or without OBSCN truncating variants shared similar demographic and echocardiographic variables at baseline. During 3.3±2.4 years (4795 patient-years) follow-up, the patients with OBSCN truncating variants were more likely to experience cardiovascular death (adjusted hazard ratio, 3.1 [95% CI, 1.40-6.70], P=0.005) and all-cause death (adjusted hazard ratio, 2.63 [95% CI, 1.21-5.71], P=0.015).CONCLUSIONS:Our data indicated that OBSCN truncating variants contributed to the disease-onset of HCM, and increased the risk of malignant events in patients with HCM.

[Incidence of coronary artery disease and outcome of patients with left ventricular noncompaction].

OBJECTIVE:To analyze the incidence of coronary artery disease (CAD) and outcome of patients with left ventricular noncompaction (LVNC).METHODS:Fifty-one patients with LVNC evaluated by echocardiography and/or cardiac magnetic resonance (CMR) from January 2006 to August 2010 were retrospectively reviewed. Coronary angiography or MDCT was performed for detecting coronary artery disease. Predictors of the cardiac events were analyzed by Cox regression analysis.RESULTS:There were 31 LVNC patients without CAD and 20 LVNC patients with CAD including single vessel coronary disease in 9 cases, double vessel coronary disease in 3 cases, three vessel coronary disease in 5 cases and left main coronary disease in 3 cases. Coronary artery bypass graft and percutaneous coronary intervention (PCI) were performed in 4 patients. Compared to LVNC patients without CAD, mean age (P = 0.008), incidence of hypertension (65.0% vs. 19.4%, P = 0.001), diabetes mellitus (40.0% vs. 12.9%, P = 0.026) and hyperlipidemia (55.0% vs. 25.8%, P = 0.035) were significantly higher while NT-proBNP level was significantly lower (P = 0.049) in LVNC patients with CAD. Incidence of major cardiac events was similar in LVNC patients with or without CAD. LogNT-proBNP is the independent prognostic factor for adverse cardiac events in patients with LVNC (HR 3.993, 95%CI 1.140 - 13.988, P = 0.030).CONCLUSIONS:Coronary artery disease is common in patients with LVNC and associated with traditional risk factors for CAD. Poor prognosis is associated with increased NT-proBNP but not with CAD in this patient cohort.

Does NT-proBNP remain a sensitive biomarker for chronic heart failure after administration of a beta-blocker?

BACKGROUND:Beta-blockers exert complex effects on plasma N-terminal-pro-B-type natriuretic peptide (NT-proBNP) level.HYPOTHESIS:We aimed to investigate whether NT-proBNP was still able to mirror the severity of chronic heart failure and predict the prognosis of the disease after administration of a beta-blocker.METHODS:Forty-four patients with chronic congestive heart failure were enrolled in the study to randomly receive carvedilol or bisoprolol in addition to background therapy. These patients underwent clinical measurement and blood sampling for NT-proBNP measurement at baseline and 3 or 7 months after the addition of the beta-blocker. The patients were followed-up for 3 years in order to register the occurrence of all-cause death.RESULTS:NT-proBNP level showed a positive correlation with the severity of heart failure as evaluated by New York Heart Association (NYHA) classification both before and after administration of either beta-blocker. The relationship between NT-proBNP and NYHA class was not weakened with the duration of therapy. Furthermore, NT-proBNP was the only independent predictor of all-cause mortality both before and after administration of either beta-blocker. Left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter (LVEDD), age, NYHA class and treatment group were not independently predictive of mortality in this study.CONCLUSIONS:The ability of NT-proBNP to reflect the severity and to predict the endpoint in chronic heart failure is not undermined after administration of a beta-blocker, suggesting that NT-proBNP remains a sensitive biomarker for chronic heart failure both before and after administration of a beta-blocker.