Clinical outcomes of subcutaneous implantable cardiac defibrillator implantation - Iran SICD registry.

BACKGROUND: The subcutaneous implantable-defibrillator (S-ICD) is a relatively new alternative to the transvenous ICD system to minimize intravascular lead-related complications. This paper presents outcome of SICD implantation in patients enrolled in Iran S-ICD registry. METHODS: Between October 2015 and June 2022, this prospective multicenter national registry included 223 patients with a standard indication for an ICD, who neither required bradycardia pacing nor needed cardiac resynchronization to evaluate the early post-implant complications and long-term follow-up results of the S-ICD system. RESULTS: The mean age of the patients was 45 ± 17 years. The majority (79.4%) were male. Ischemic cardiomyopathy (39.5%) was the most common underlying disorder among patients selected for S-ICD implant. Most study patients (68.6%) had ICD for primary prevention of sudden cardiac death. Seven patients (3.1%) were found to have suboptimal lead positions. Six patients (2.7%) developed a pocket hematoma; all were managed medically. During a mean follow-up of 2 years, the appropriate therapy was recorded in 13% of the patients and inappropriate ICD intervention mainly due to supraventricular tachycardia in 8.9%. Pocket infection was observed in four patients (1.8%) and five patients (2.2%) died mainly due to heart failure. CONCLUSION: S-ICDs were effective at detecting and treating both induced and spontaneous ventricular arrhythmias. Major clinical complications were rare.

Cardiomyopathy with lethal arrhythmias associated with inactivation of KLHL24.

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disorder, yet the genetic cause of up to 50% of cases remains unknown. Here, we show that mutations in KLHL24 cause HCM in humans. Using genome-wide linkage analysis and exome sequencing, we identified homozygous mutations in KLHL24 in two consanguineous families with HCM. Of the 11 young affected adults identified, 3 died suddenly and 1 had a cardiac transplant due to heart failure. KLHL24 is a member of the Kelch-like protein family, which acts as substrate-specific adaptors to Cullin E3 ubiquitin ligases. Endomyocardial and skeletal muscle biopsies from affected individuals of both families demonstrated characteristic alterations, including accumulation of desmin intermediate filaments. Knock-down of the zebrafish homologue klhl24a results in heart defects similar to that described for other HCM-linked genes providing additional support for KLHL24 as a HCM-associated gene. Our findings reveal a crucial role for KLHL24 in cardiac development and function.

Comparison of de novo implantation vs. upgrade cardiac resynchronisation therapy: a multicentre experience.

BACKGROUND: The clinical safety and consequences of upgrade procedures compared with de novo cardiac resynchronisation therapy (CRT) implantation in heart failure remain unclear. The present study aimed to assess clinical and procedural consequences of patients undergoing CRT upgrade as compared to de novo CRT implantations. METHODS: In this prospective cohort study, two subgroups were considered as the study population as (1) de novo group that CRT was considered on optimised medical treatment with heart failure of NYHA functional class from II to IV, left ventricular ejection fraction (LVEF) of ≤35%, and QRS width of >130 ms and (2) upgrade group including the patients with previously implantable cardioverter defibrillator (ICD) with the indications for upgrading to CRT. The two groups were compared regarding the changes in clinical outcome and echocardiography parameters. RESULTS: The procedure was successful in 95.9% of patients who underwent CRT upgrade and 100% of those who underwent de novo CRT implantation. It showed a significant improvement in LVEF, severity of mitral regurgitation and NYHA functional classification, without any difference between the two study groups. Overall procedural related complications were reported in 10.8% and 3.8% (p = .093) and cardiac death in 5.4% and 2.5% (p = .360), respectively, with no overall difference in postoperative outcome between the two groups. CONCLUSIONS: Upgrading to CRT is a safe and effective procedure regarding improvement of functional class, left ventricular function status and post-procedural outcome.

Genetic Insights from Consanguineous Cardiomyopathy Families.

Inherited cardiomyopathies are a prevalent cause of heart failure and sudden cardiac death. Both hypertrophic (HCM) and dilated cardiomyopathy (DCM) are genetically heterogeneous and typically present with an autosomal dominant mode of transmission. Whole exome sequencing and autozygosity mapping was carried out in eight un-related probands from consanguineous Middle Eastern families presenting with HCM/DCM followed by bioinformatic and co-segregation analysis to predict the potential pathogenicity of candidate variants. We identified homozygous missense variants in TNNI3K, DSP, and RBCK1 linked with a dilated phenotype, in NRAP linked with a mixed phenotype of dilated/hypertrophic, and in KLHL24 linked with a mixed phenotype of dilated/hypertrophic and non-compaction features. Co-segregation analysis in family members confirmed autosomal recessive inheritance presenting in early childhood/early adulthood. Our findings add to the mutational spectrum of recessive cardiomyopathies, supporting inclusion of KLHL24, NRAP and RBCK1 as disease-causing genes. We also provide evidence for novel (recessive) modes of inheritance of a well-established gene TNNI3K and expand our knowledge of the clinical heterogeneity of cardiomyopathies. A greater understanding of the genetic causes of recessive cardiomyopathies has major implications for diagnosis and screening, particularly in underrepresented populations, such as those of the Middle East.

ST-segment depression as a risk factor in hypertrophic cardiomyopathy.

AIMS: From the spectrum of electrocardiogram (ECG) changes that may occur in hypertrophic cardiomyopathy (HCM), there is no criterion reported to be useful for risk stratification. We sought to determine whether there was a relationship between the resting ECG findings and prognosis in patients with HCM. METHODS AND RESULTS: We retrospectively analysed data on 173 consecutive patients admitted to our centre with a diagnosis of HCM. The 12-lead ECGs were assessed for underlying rhythm, PR interval, QRS voltages, QRS width, corrected QT interval, ST-segment deviation, T-wave inversion, and left atrial enlargement (LAE). During a mean follow-up of 50 months, 6.4% of patients had a combined endpoint [sudden death or appropriate implantable cardioverter-defibrillator (ICD) therapy]. The frequency of the combined endpoint was greater in patients with syncope, non-sustained ventricular tachycardia, maximal left ventricular (LV) wall thickness >or=30 mm, and ST-segment depression in the high lateral leads (all P < 0.05). Other ECG findings (LV hypertrophy, LAE, abnormal Q wave, abnormal ST-T changes, and underlying rhythm), family history of sudden death, and LV outflow obstruction were not related to the combined endpoint. The results of our multivariate analysis demonstrated that ST-segment depression in the high lateral leads (OR: 20.0, 95% CI: 12.7-27.5; P = 0.0001) and syncope (OR: 19.0, 95% CI: 11.7-26.9; P = 0.0001) were the predictors of sudden death or appropriate ICD therapy in patients with HCM. CONCLUSION: The results of this study indicated that, in addition to generally accepted risk factors, ST-segment depression in the high lateral leads could be of prognostic significance in HCM patients.

Predictors of syncope in patients with hypertrophic cardiomyopathy.

BACKGROUND: Approximately 30% of patients with hypertrophic cardiomyopathy (HCM) suffer syncope and syncope was the only symptom associated with sudden death. However, no systematic studies in large cohorts looking at predictors of syncope are available in the literature. Therefore, we sought to determine predictors of syncope in patients with HCM. METHODS: One hundred and seventy-three consecutive patients with HCM and a mean age of 42 +/- 18 years (range 10-78) underwent extensive clinical, electrocardiographic, and echocardiographic testing to identify predictors of syncope. RESULTS: During the mean follow-up duration of 50 months, syncope occurred in 28% of the HCM patients. Univariate analysis showed male gender, age <40 years, family history of sudden death, PR interval, QRS width, >or=2 bursts of nonsustained ventricular tachycardia (NSVT), >or=3 bursts of nonsustained supraventricular tachycardia (NSSVT), maximum left ventricular wall thickness >or=30 mm, and abnormal blood pressure response, out of 24 demographic, clinical, hemodynamic, electrocardiographic, and echocardiographic features, to be significantly associated with syncope. Of these nine variables, the only independent predictors of syncope at multivariate analysis were age <40 years (odds ratio [OR]: 4.4, 95% confidence interval [CI]: 2.2-16, P = 0.003), >or=2 bursts of NSVT (OR: 9.9, 95% CI: 2.0-46, P = 0.0001), and >or=3 bursts of NSSVT (OR: 2.7, 95% CI: 0.38-8.25, P = 0.001). The concomitant occurrence of all three variables had a sensitivity of 87% and specificity of 73% in identifying the patients with syncopal events. CONCLUSIONS: The results of this study showed that age <40 years, bursts of NSVT, and NSSVT were independently associated with the risk of syncope in patients with HCM. Demographic data and ambulatory ECG findings could help in risk stratification of patients with HCM.

Clinical value and severity of myocardial perfusion defects in asymptomatic diabetic patients with negative or weakly positive exercise treadmill test.

OBJECTIVE: Although coronary artery disease (CAD) is the leading cause of death in type 2 diabetic patients, it is frequently asymptomatic. Myocardial perfusion imaging (MPI) is reported to show ischemia in a significant number of asymptomatic diabetic patients. We studied the prevalence and severity of myocardial perfusion defects in asymptomatic diabetic patients and its clinical impact. METHODS AND PATIENTS: One hundred thirty consecutive asymptomatic patients, aged 35-65 years with type 2 diabetes mellitus and with no history of CAD and no cardiac symptoms were recruited in the study. Echocardiography, electrocardiography (ECG), routine laboratory tests and exercise treadmill test (ETT) were performed and patients with weakly positive or negative ETT underwent Dipyridamole MPI. Patients with positive ETT were referred to coronary angiography. Patients were followed for at least 17 months (mean 21.7 months) and any cardiac event was recorded. RESULTS: We studied 81 female and 49 male patients with mean age of 51.8 years. Negative, weakly positive and positive ETT result was noted in 74.3%, 15% and 10.7% respectively. 75% of patients with positive ETT had coronary artery disease in angiography. Gated myocardial perfusion SPECT was done in 106 patients. MPI showed reversible defect in 26.9% of the patients with a mean summed stress score of 3.3±1.8. Follow up completed in 112 patients and only one patient with abnormal MPI underwent coronary angiography followed by PTCA. No cardiac death, MI, UA or hospital admission occurred among our patients during follow up (17-26 months). Mean stress end diastolic volume (EDV) was significantly higher in patients with reversible defect compared to patients without reversible defect based on MPI findings (62.0±31.6 Vs 48.5±18.4 ml, P=0.04). Blood glucose and HbA1c were significantly higher in patients with ischemia compared to patients without ischemia (P<0.05). Meanwhile the ratio of TG to HDL was 6.06±3.2 in ischemic patients compared to 4.8±2.3 in normal subjects (P=0.03). CONCLUSION: Reversible defects are commonly seen in myocardial perfusion SPECT in asymptomatic diabetic patients and are mild in severity and not associated with adverse cardiac events. Routine approach for detection of CAD beginning with ETT seems to be appropriate in these patients.

Electrocardiographic changes after dipyridamole infusion in patients undergoing myocardial perfusion imaging.

OBJECTIVES: Although the diagnostic and prognostic importance of perfusion defects has been clearly established, the meaning of the development and characteristics of electrocardiographic (ECG) changes during dipyridamole infusion is less well defined. This study tries to evaluate the prevalence and significance of ECG changes after dipyridamole infusion and their relation to ischemia in myocardial perfusion single-photon emission computed tomography (SPECT). METHODS: Two hundred patients underwent 2-day dipyridamole stress/rest Tc-99m-sestamibi myocardial perfusion SPECT. Basal and post dipyridamole ECGs were analyzed. Myocardial perfusion images were interpreted visually and semiquantitatively. RESULTS: New ECG changes were noted in 20.2% of cases and consisted of 1.1% T-wave flattening, 1.1% T-wave inversion and 14.8% ST depression and 4.2% psuedonormalization. Abnormal ECG changes were noted after dipyridamole infusion in approximately 27.7% of patients with and 14.3% of patients without reversible defect in myocardial perfusion SPECT. A new ST depression was noted in lateral leads in 72.2% of new ST changes. The mean post-dipyridamole heart rate increment in patients with reversible or partially reversible defects was significantly lesser than in patients with normal myocardial perfusion SPECT. In addition, the corrected QT interval (QTc) increment in patients with reversible defects was significantly more than in patients with fixed defects; however, there was no difference when compared with patients with no defects. Using linear regression model, the severity of ST depression and QTc increment were significant predictors of summed difference score. Sensitivity, specificity, and negative and positive predictive values of ST-segment depression for the diagnosis of ischemia were 20.2, 89.5, 60.7, and 58.4%, respectively. CONCLUSION: The most common ECG change seen after dipyridamole infusion is ST-segment depression. The new ST-segment depression after dipyridamole infusion is highly specific for ischemia. Reversible defects are associated with a lesser increment in heart rate, whereas QTc increment and severity of ST segment depression were significant predictors of summed difference score.